Cancer Immunology Research

Cancer Immunol Res. 2025 Aug 29. doi: 10.1158/2326-6066.CIR-25-0083. Online ahead of print. ABSTRACT Polymerase epsilon mutant (POLE-mut) endometrial cancers (EC) are characterized by a near 100% disease-specific survival rate, even when treated by surgery alone. This spectacular survival, combined with the ultramutated genome and high level of neoantigens in these tumors, indicates a substantial degree … Read more

Cancer Immunol Res. 2025 Aug 29. doi: 10.1158/2326-6066.CIR-25-0047. Online ahead of print. ABSTRACT Immunotherapy has emerged as a promising treatment for head and neck squamous cell carcinoma (HNSCC), yet clinical responses remain limited. Elevated expression of interferon-stimulated gene 15 (ISG15), commonly observed in oral squamous cell carcinoma (OSCC), may contribute to this limited efficacy. Although … Read more

Cancer Immunol Res. 2025 Aug 28. doi: 10.1158/2326-6066.CIR-24-0835. Online ahead of print. ABSTRACT While immune checkpoint inhibitors have led to durable responses in various cancer types, a substantial proportion of patients do not respond to these interventions. To uncover potential factors associated with a positive response to immunotherapy, we used a bilateral tumor model using … Read more

Cancer Immunol Res. 2025 Aug 28. doi: 10.1158/2326-6066.CIR-25-0159. Online ahead of print. ABSTRACT Myeloid cells – including monocytes, macrophages, dendritic cells, and granulocytes – are critical architects of the tumor microenvironment, where they exert diverse functions ranging from immunosuppressive to immunostimulatory. Advances in single-cell omics and high-dimensional immune profiling have unveiled the remarkable heterogeneity and … Read more

Cancer Immunol Res. 2025 Aug 28. doi: 10.1158/2326-6066.CIR-25-0491. Online ahead of print. ABSTRACT Advanced sarcomas have limited treatment options after standard therapy, and therefore we investigated the efficacy and safety of sintilimab plus anlotinib in this setting. Patients aged 18-75 years with advanced sarcomas and prior systemic therapy were enrolled. Patients with untreated, primary chemotherapy-resistant … Read more

Cancer Immunol Res. 2025 Aug 20. doi: 10.1158/2326-6066.CIR-24-0902. Online ahead of print. ABSTRACT Treating radioresistant tumors like glioblastoma multiforme (GBM) remains a challenge exacerbated by their immunosuppressive nature. Radiation therapy has an immunomodulatory role, both immunosuppressive and immunostimulatory. The nature of the effects depends on the total dose, dose per fraction, dose delivery method and … Read more

Cancer Immunol Res. 2025 Aug 19. doi: 10.1158/2326-6066.CIR-25-0313. Online ahead of print. ABSTRACT T-cell therapies have transformed cancer treatment. While surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell-mediated tumor immunity remains an area of active investigation. In this study, we … Read more

Cancer Immunol Res. 2025 Aug 19. doi: 10.1158/2326-6066.CIR-25-0031. Online ahead of print. ABSTRACT Early synchronous colorectal liver metastasis (CRLM) represents a clinical condition characterized by the simultaneous presence of primary colorectal cancer (CRC) and metastatic liver lesions. In this study, we characterized the tissue-specific transcriptomes, phenotypes, and functional relevance of tumor-associated macrophages (TAMs) within the … Read more

Cancer Immunol Res. 2025 Aug 18:OF1-OF6. doi: 10.1158/2326-6066.CIR-25-0384. Online ahead of print. ABSTRACT The effectiveness of T cell-based immunotherapy depends on durable T-cell responses that can efficiently eliminate tumor cells. NKG7 was discovered three decades ago as a protein associated with lytic granules. However, only studies published over the past 5 years have contributed substantially … Read more

Cancer Immunol Res. 2025 Aug 15. doi: 10.1158/2326-6066.CIR-25-0387. Online ahead of print. ABSTRACT Pancreatic adenocarcinoma (PDAC) is a rapidly progressing cancer that responds poorly to immunotherapies. Intratumoral tertiary lymphoid structures (TLS) have been associated with rare long-term PDAC survivors, but the role of TLS in PDAC and their spatial relationships within the context of the … Read more

Cancer Immunol Res. 2025 Aug 8:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-0624. Online ahead of print. ABSTRACT Anaplastic lymphoma kinase-rearranged lung adenocarcinoma (ALK+ LUAD) is currently considered an immune-resistant disease, yet underlying biological mechanisms are largely unknown. In this issue, Arai and colleagues analyzed the tumor microenvironment (TME) in ALK+ LUADs, identifying a myeloid cell-dominant immunosuppressive TME, primarily driven … Read more

Cancer Immunol Res. 2025 Aug 7. doi: 10.1158/2326-6066.CIR-24-1163. Online ahead of print. ABSTRACT Recent studies have explored the composition of tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL) However, cell-to-cell interactions, along with the spatial organization of DLBCL TME and their impact on patient outcomes, have remained poorly characterized. We ap-plied multiplexed immunofluorescence, cell … Read more

Cancer Immunol Res. 2025 Aug 4. doi: 10.1158/2326-6066.CIR-24-0927. Online ahead of print. ABSTRACT Antigen presentation by dendritic cells (DCs) is crucial in activating T-cells. DCs capture, process, and present antigens to T-cells, making them attractive vaccine vehicles. However, most DC cancer vaccines have had limited clinical efficacy, suggesting a need to increase their potency. We … Read more

Cancer Immunol Res. 2025 Aug 1. doi: 10.1158/2326-6066.CIR-24-1088. Online ahead of print. ABSTRACT Macrophages expressing Trem2 play a pivotal role in promoting non-alcoholic steatohepatitis (NASH; also known as metabolic dysfunction-associated steatohepatitis, MASH) progression to hepatocellular carcinoma (HCC). Despite the widespread clinical use of anti-PD1 immune checkpoint blockade, its therapeutic efficacy in NASH-driven HCC remains suboptimal. … Read more

Cancer Immunol Res. 2025 Aug 1. doi: 10.1158/2326-6066.CIR-24-0897. Online ahead of print. ABSTRACT Advanced sarcomas have dismal outcomes in children and adults, with limited therapeutic options. While chimeric antigen receptor T cells (CAR-T) hold promise for treating advanced sarcomas, it is constrained by a paucity of effectual targets. Our previous clinical study identified endoglin (ENG/CD105), … Read more

Cancer Immunol Res. 2025 Aug 1;13(8):1131. doi: 10.1158/2326-6066.CIR-13-8-WWR. NO ABSTRACT PMID:40746082 | DOI:10.1158/2326-6066.CIR-13-8-WWR

Cancer Immunol Res. 2025 Jul 31. doi: 10.1158/2326-6066.CIR-24-0534. Online ahead of print. ABSTRACT Pancreatic adenocarcinoma (PDAC) has a dismal survival rate due to limited effective therapies. While studies have focused on innate immune cell influence on adaptive immune cell functions, few have explored interactions between innate immune cells, which modulate the unique PDAC tumor microenvironment … Read more

Cancer Immunol Res. 2025 Jul 31. doi: 10.1158/2326-6066.CIR-24-0853. Online ahead of print. ABSTRACT Despite the effectiveness of anti-programmed death 1 (PD-1)/PD-1 ligand 1 monoclonal antibodies against various cancers, resistance remains a significant issue among patients. The immunosuppressive T cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD155 axis has emerged as a key mechanism contributing to … Read more

Cancer Immunol Res. 2025 Jul 30. doi: 10.1158/2326-6066.CIR-24-0919. Online ahead of print. ABSTRACT Therapies using natural killer (NK) cells that express chimeric antigen receptors (CAR-NKs) have been successfully employed against hematological malignancies. However, solid tumors resist CAR NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor … Read more

Cancer Immunol Res. 2025 Jul 18. doi: 10.1158/2326-6066.CIR-24-1146. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) are key regulators of tumor immunity. With advances in single-cell analyses, SPP1+ TAMs have been observed across multiple tumor sites. However, their clinical relevance and phenotypic characteristics in clear cell renal cell carcinoma (ccRCC) have not been comprehensively delineated. … Read more

Cancer Immunol Res. 2025 Jul 8. doi: 10.1158/2326-6066.CIR-24-0532. Online ahead of print. ABSTRACT Tyrosine kinase inhibitors (TKIs) are initially efficacious against anaplastic lymphoma kinase (ALK) fusion gene-positive lung adenocarcinoma (ALK+ LUAD), but acquired resistance inevitably occurs. Therefore, alternative treatment strategies are needed for TKI-resistant cases. Although the use of immune checkpoint inhibitors (ICIs) has improved … Read more

Cancer Immunol Res. 2025 Jul 8. doi: 10.1158/2326-6066.CIR-24-1285. Online ahead of print. ABSTRACT Vγ9Vδ2 (TCRVγ9+ TCRVδ2+) T cells are promising immunotherapeutic targets with effective antitumor properties in both in vitro and preclinical models of triple-negative breast cancer (TNBC). However, no information regarding their potential role in the context of human TNBC progression and response to … Read more

Cancer Immunol Res. 2025 Jul 2. doi: 10.1158/2326-6066.CIR-25-0103. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are major immune components of the tumor microenvironment, promoting tumor growth and limiting the efficacy of chemotherapy in almost all cancer indications. While Tregs are well known for their immune suppressive activity toward the … Read more

Cancer Immunol Res. 2025 Jul 2. doi: 10.1158/2326-6066.CIR-25-0034. Online ahead of print. ABSTRACT Dendritic cell (DC) based-vaccines remain the sole approved cancer vaccine. Despite their established safety and efficacy in numerous trials against cancers and infections, long-term clinical benefits have been modest. Most trials have employed DCs derived from blood monocytes (MoDC), but emerging evidence … Read more

Cancer Immunol Res. 2025 Jul 2;13(7):963. doi: 10.1158/2326-6066.CIR-13-7-WWR. NO ABSTRACT PMID:40598952 | DOI:10.1158/2326-6066.CIR-13-7-WWR

Cancer Immunol Res. 2025 Jul 1. doi: 10.1158/2326-6066.CIR-24-1144. Online ahead of print. ABSTRACT Cancer-associated fibroblasts (CAFs) play immunosuppressive roles in the tumor microenvironment (TME). Specifically, they reportedly act as physical barriers preventing immune cell infiltration. However, the spatial relationships between CAFs and cancer cells in antitumor immunity remain unknown. In this study, we established three-dimensional … Read more

Cancer Immunol Res. 2025 Jul 1. doi: 10.1158/2326-6066.CIR-24-1109. Online ahead of print. ABSTRACT The blood T cell receptor (TCR) repertoire broadly reflects current and lifetime immune responses against infectious pathogens and cancer, but the circulating T cell repertoire remains a largely untapped resource for cancer biomarker studies due to repertoire complexity and limited profiling data. … Read more

Cancer Immunol Res. 2025 Jun 27. doi: 10.1158/2326-6066.CIR-24-1313. Online ahead of print. ABSTRACT Anti-BCMA CAR-T cell therapy has revolutionized the prognosis of relapsed / refractory multiple myeloma patients. Regrettably, despite unprecedented overall response rates achieved with this approach, most patients eventually relapse. One of the primary reasons for this is the complete loss or reduced … Read more

Cancer Immunol Res. 2025 Jun 26. doi: 10.1158/2326-6066.CIR-24-0091. Online ahead of print. ABSTRACT Acquired mutations in spliceosome genes in early hematopoietic stem/progenitor cells are common events in myelodysplastic neoplasms (MDS) and related myeloid malignancies. Mutations in the spliceosome factor subunit B1 (SF3B1) gene occur in ≥20% of MDS cases at conserved hotspots and in early … Read more

Cancer Immunol Res. 2025 Jun 26. doi: 10.1158/2326-6066.CIR-24-0975. Online ahead of print. ABSTRACT Neuroblastoma (NB) is a highly aggressive childhood solid tumor with poor outcomes. Chimeric antigen receptor (CAR) T cells have shown limited efficacy in NB, with the best outcomes reported in patients with a low tumor burden, highlighting the need for further CAR … Read more

Cancer Immunol Res. 2025 Jun 18. doi: 10.1158/2326-6066.CIR-24-1128. Online ahead of print. ABSTRACT The retinoic acid receptor-related orphan receptor C (RORC) gene encodes two isoforms, RORγ and RORγt, which function as transcription factors in different cell types. RORγt is expressed in specific immune cells involved in inflammatory responses, while RORγ is found in parenchymal cells, … Read more

Cancer Immunol Res. 2025 Jun 16. doi: 10.1158/2326-6066.CIR-24-1233. Online ahead of print. ABSTRACT Tumour-associated macrophages (TAMs) are a universal feature of cancers but variably influence outcome and treatment responses. Here, we used a photoconvertible mouse to distinguish newly entering, monocyte-derived (md)TAMs that were enriched at the tumour core, from resident-like (r)TAMs that localised with fibroblasts … Read more

Cancer Immunol Res. 2025 Jun 13. doi: 10.1158/2326-6066.CIR-24-0519. Online ahead of print. ABSTRACT Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants resistant … Read more

Cancer Immunol Res. 2025 Jun 12. doi: 10.1158/2326-6066.CIR-24-1001. Online ahead of print. ABSTRACT NK cells are increasingly being evaluated for their utility in cancer immunotherapy. However, their efficacy is often attenuated in the cancer microenvironment. The identification of additional checkpoint molecules that limit NK-cell function is crucial to further development of NK cell-based therapies. Herein, … Read more

Cancer Immunol Res. 2025 Jun 12. doi: 10.1158/2326-6066.CIR-25-0156. Online ahead of print. ABSTRACT Diacylglycerol kinase α (DGKα) and DGKζ are lipid kinases that negatively regulate T-cell signaling through diacylglycerol (DAG) metabolism, making them attractive targets for next-generation immunotherapy. Here, we report the discovery and pre-clinical characterization of the clinical-stage DGKα and DGKζ lipid kinase inhibitor, … Read more

Cancer Immunol Res. 2025 Jun 10:OF1-OF14. doi: 10.1158/2326-6066.CIR-24-1270. Online ahead of print. ABSTRACT The rapid advancement of artificial intelligence (AI) technologies has opened new avenues for advancing personalized immunotherapy in cancer treatment. This review highlights current research progress in applying AI to optimize the use of immunotherapy for patients with cancer. Recent studies demonstrate that … Read more

Cancer Immunol Res. 2025 Jun 5. doi: 10.1158/2326-6066.CIR-24-0797. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 … Read more

Cancer Immunol Res. 2025 Jun 4;13(6):791. doi: 10.1158/2326-6066.CIR-13-6-WWR. NO ABSTRACT PMID:40462592 | DOI:10.1158/2326-6066.CIR-13-6-WWR

Cancer Immunol Res. 2025 Jun 3. doi: 10.1158/2326-6066.CIR-24-0467. Online ahead of print. ABSTRACT Cytotoxic T-lymphocytes (CTLs) screen cells for signs of infection and transformation by recognizing peptides displayed on major histocompatibility complex (MHC) class I molecules. Next to canonical ATG-initiated open reading frames (ORFs), non-canonical translation can result in synthesis of non-conventional or `cryptic´ polypeptides. … Read more

Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-0876. Online ahead of print. ABSTRACT CAR T-cell therapy is an effective treatment strategy in B-cell malignancies, however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature, however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic … Read more

Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-1298. Online ahead of print. ABSTRACT Analysis of post-translational modifications (PTMs) of proteins can provide new insight, beyond that obtained from analysis of protein levels, for understanding the tumor microenvironment (TME). The characteristics of PTMs in immune cells, along with their spatial distribution, have not been comprehensively integrated, … Read more

Cancer Immunol Res. 2025 May 29. doi: 10.1158/2326-6066.CIR-24-1191. Online ahead of print. ABSTRACT Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90Y, 177Lu, and 225Ac in vitro as unbound radionuclides and … Read more

Cancer Immunol Res. 2025 May 29. doi: 10.1158/2326-6066.CIR-24-0137. Online ahead of print. ABSTRACT Gastrointestinal cancers (GICs), including gastric cancers (GCs) and colorectal cancers (CRCs), are among the leading causes of cancer-related deaths worldwide. Metastatic GCs and CRCs often develop resistance or fail to respond to current therapies. Adoptive T-cell immunotherapy, especially with T cells expressing … Read more

Cancer Immunol Res. 2025 May 22. doi: 10.1158/2326-6066.CIR-24-0405. Online ahead of print. ABSTRACT Significant progress in the application of immune checkpoint blockade (ICB) for the treatment of multiple types of cancers has been achieved, but its overall response rate and therapeutic efficacy remain unsatisfactory. To address these limitations, the identification of a combinational approach to … Read more

Cancer Immunol Res. 2025 May 22. doi: 10.1158/2326-6066.CIR-24-0937. Online ahead of print. ABSTRACT IgM antibodies are preformed pentameric or hexameric molecules that can be engineered to generate high affinity and high avidity fully human antibody therapeutics. In this study, we report an immunocytokine, IGM-7354, which was designed to bind multiple PD-L1 receptors while trans-presenting a … Read more

Cancer Immunol Res. 2025 May 19. doi: 10.1158/2326-6066.CIR-24-0119. Online ahead of print. ABSTRACT The efficacy of most immunotherapies for prostate cancer is limited by poor tumor immunogenicity, evidenced by minimal T-cell infiltration. Treatment with T cells engineered to express T-cell receptors (TCR) targeting prostate-specific antigens offers a potential solution by bypassing endogenous T-cell repertoire limitations. … Read more

Cancer Immunol Res. 2025 May 19:OF1-OF12. doi: 10.1158/2326-6066.CIR-24-1192. Online ahead of print. ABSTRACT Endogenous retroviruses (ERV) are the genetic remnants of retroviruses in which proviral sequences integrated into germline cells of our ancestors. Although the vast majority of ERV sequences have accumulated mutations over the course of human evolution, some still contain open reading frames … Read more

Cancer Immunol Res. 2025 May 8. doi: 10.1158/2326-6066.CIR-25-0019. Online ahead of print. ABSTRACT A key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why that is. Here, we … Read more

Cancer Immunol Res. 2025 May 5. doi: 10.1158/2326-6066.CIR-24-0419. Online ahead of print. ABSTRACT Immune evasion is a hallmark of gliomas, yet the genetic mechanisms by which tumors escape immune surveillance remain incompletely understood. In this study, we systematically examined the presence of somatic mutations in human leukocyte antigen (HLA) genes and genes encoding proteins involved … Read more

Cancer Immunol Res. 2025 May 5. doi: 10.1158/2326-6066.CIR-24-1194. Online ahead of print. ABSTRACT Colorectal cancer (CRC) creates a suppressive tumor immune microenvironment (TIME) which leads to tumor progression and resistance to immune checkpoint inhibitor (ICI) therapy. Ubiquitin-specific peptidase 15 (USP15) broadly regulates immune responses and immune cell differentiation, but its involvement in shaping the TIME … Read more

Cancer Immunol Res. 2025 May 2;13(5):617. doi: 10.1158/2326-6066.CIR-13-5-WWR. NO ABSTRACT PMID:40313108 | DOI:10.1158/2326-6066.CIR-13-5-WWR

Cancer Immunol Res. 2025 Apr 29. doi: 10.1158/2326-6066.CIR-24-1179. Online ahead of print. ABSTRACT The efficacy of immunotherapy targeting PD-1/PD-L1 in gastric cancer (GC) depends on PD-L1 expression level and infiltration of immune cells within the tumor microenvironment (TME). While methyltransferase-like 3 (METTL3) plays a role in the development and progression of GC, its mechanism of … Read more

Cancer Immunol Res. 2025 Apr 29:OF1-OF14. doi: 10.1158/2326-6066.CIR-24-1347. Online ahead of print. ABSTRACT Patients can develop human anti-mouse immune responses against CD19-specific chimeric antigen receptor (CAR) T cells due to the use of a murine CD19-specific single-chain variable fragment to redirect T cells. We screened a yeast display library to identify an array of fully … Read more

Cancer Immunol Res. 2025 Apr 28. doi: 10.1158/2326-6066.CIR-24-0852. Online ahead of print. ABSTRACT Adaptive Natural Killer (aNK) cells have emerged as a subset of NK cells with memory-like properties and specific cytotoxicity, offering promising therapeutic potential in cancer immunotherapy. In this study, we explored the role of aNK cells in high-grade serous ovarian cancer (HGSOC), … Read more

Cancer Immunol Res. 2025 Apr 22. doi: 10.1158/2326-6066.CIR-24-0306. Online ahead of print. ABSTRACT Spontaneous remission in patients with various cancers has been reported. Some patients with adult T-cell leukemia-lymphoma (ATL), have experienced spontaneous remission, although mechanisms for this remain unknown. In this study, we analyzed ATL cells and human T-cell leukemia virus type 1 (HTLV-1) … Read more

Cancer Immunol Res. 2025 Apr 22. doi: 10.1158/2326-6066.CIR-24-0127. Online ahead of print. ABSTRACT NEDDylation is a post-translational modification whereby the ubiquitin-like molecule NEDD8 is attached to protein substrates in a process dependent on NEDD8 activating enzyme regulatory subunit (NAE1). NEDDylation is emerging as a regulator of cancer biology, but its precise role in antitumor immunity … Read more

Cancer Immunol Res. 2025 Apr 18. doi: 10.1158/2326-6066.CIR-24-0387. Online ahead of print. ABSTRACT Although initially assumed to be similar, immune checkpoint inhibitor (ICI)-induced autoimmunity can differ from spontaneous autoimmune disease regarding clinical presentation, pathogenesis and therapy. Despite limited pathogenetic understanding, ICI-induced colitis (irColitis), a common adverse event during ICI therapy, is treated analogously to its … Read more

Cancer Immunol Res. 2025 Apr 18:OF1-OF20. doi: 10.1158/2326-6066.CIR-24-0630. Online ahead of print. ABSTRACT Detection of disseminated cancer cells (DCC) in the bone marrow (BM) of patients with breast cancer is a critical predictor of late recurrence and distant metastasis. Conventional therapies often fail to completely eradicate DCCs in patients. In this study, we demonstrate that … Read more

Cancer Immunol Res. 2025 Apr 16. doi: 10.1158/2326-6066.CIR-24-1050. Online ahead of print. ABSTRACT CAR T-cell therapy has improved outcomes for patients with chemotherapy-resistant B-cell malignancies. However, CAR T-cell treatment of patients with solid cancers has been more difficult, in part because of the heterogeneous expression of tumor-specific cell surface antigens. Here, we describe the generation … Read more

Cancer Immunol Res. 2025 Apr 15:OF1-OF15. doi: 10.1158/2326-6066.CIR-24-0894. Online ahead of print. ABSTRACT T-cell senescence occurs in the tumor microenvironment (TME) and influences cancer outcomes, as well as the effectiveness of immunotherapies. The TME triggers this T-cell senescence via multiple pathways, including persistent stimulation with tumor-associated antigens, altered metabolic pathways, and activation of chronic inflammatory … Read more

Cancer Immunol Res. 2025 Apr 11. doi: 10.1158/2326-6066.CIR-24-0333. Online ahead of print. ABSTRACT The optimal means to prime for effective anti-tumor immunity in a cancer patient remains elusive in the current era of checkpoint blockade. Crafting a strategy to amplify CD8+ T cells while blocking regulatory cells should increase immunotherapy efficacy. Biomaterial carriers have been … Read more

Cancer Immunol Res. 2025 Apr 10. doi: 10.1158/2326-6066.CIR-24-0807. Online ahead of print. ABSTRACT The lack of response of glioblastoma (GBM) to immunotherapy is closely related to the limited number of T cells in the tumor microenvironment (TME). However, it is still not known why GBM is characterized by an immune-cold TME with reduced CD8+ T-cell … Read more

Cancer Immunol Res. 2025 Apr 2;13(4):453. doi: 10.1158/2326-6066.CIR-13-4-WWR. NO ABSTRACT PMID:40170562 | DOI:10.1158/2326-6066.CIR-13-4-WWR

Cancer Immunol Res. 2025 Apr 1. doi: 10.1158/2326-6066.CIR-24-0746. Online ahead of print. ABSTRACT Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a molecularly distinct tyrosine kinase-driven cancer that has a high relapse rate and poor response toward combinatorial chemotherapy. Tyrosine kinase inhibitors (TKI) in the clinic improve the survival of patients with Ph-like ALL. Engineered antibody … Read more

Cancer Immunol Res. 2025 Apr 1. doi: 10.1158/2326-6066.CIR-24-0834. Online ahead of print. ABSTRACT Local immunotherapy stimulates immune responses against tumors while avoiding adverse effects associated with systemic administration. However, current strategies for tumor-targeted in situ immunotherapy are still limited. mRNA-based gene therapy represents a promising strategy. Gasdermin E (GSDME)-mediated pyroptosis is reported to exert anti-tumor … Read more

Cancer Immunol Res. 2025 Apr 1. doi: 10.1158/2326-6066.CIR-24-0598. Online ahead of print. ABSTRACT Memory-phenotype (MP) CD4+ T lymphocytes spontaneously develop in steady state from peripheral naïve precursors in a manner dependent on self-antigen recognition. While MP cells possess innate type 1 and 3 effector functions that can contribute to host defense and autoimmunity, their immunological … Read more

Cancer Immunol Res. 2025 Mar 27. doi: 10.1158/2326-6066.CIR-24-1055. Online ahead of print. ABSTRACT The systemic immunological effects of combining anti-CTLA4 therapy with PD-(L)1 blockade remain incompletely characterized, despite the widespread use of this combination in treating various solid tumors across multiple stages of disease. Herein, we investigated the additive impact of anti-CTLA4 on peripheral immune … Read more

Cancer Immunol Res. 2025 Mar 27. doi: 10.1158/2326-6066.CIR-24-0737. Online ahead of print. ABSTRACT Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of cancer patients. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. Here, we … Read more

Cancer Immunol Res. 2025 Mar 25. doi: 10.1158/2326-6066.CIR-24-0743. Online ahead of print. ABSTRACT Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma (GBM) and other World Health Organization (WHO) grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP … Read more

Cancer Immunol Res. 2025 Mar 14:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-0202. Online ahead of print. ABSTRACT Biomarkers of responsiveness to immune checkpoint blockade (ICB) are heavily sought given the breadth and depth of the use of ICB in cancer. PD-L1 expression was among the first biomarkers identified, but multiple factors have precluded more widespread use. In this issue, … Read more

Cancer Immunol Res. 2025 Mar 14:OF1-OF20. doi: 10.1158/2326-6066.CIR-24-0151. Online ahead of print. ABSTRACT Immunotherapies have had unprecedented success in the treatment of multiple cancer types, albeit with variable response rates. Unraveling the complex network of immune cells within the tumor microenvironment (TME) may provide additional insights to enhance antitumor immunity and improve clinical response. Many … Read more

Cancer Immunol Res. 2025 Mar 12. doi: 10.1158/2326-6066.CIR-24-0758. Online ahead of print. ABSTRACT Agonistic anti-CD40 with anti-PD-1 can elicit objective responses in a small number of patients with pancreatic ductal adenocarcinoma (PDA). Better understanding of their individual effects on the PDA tumor microenvironment will help inform new strategies to further improve outcomes. Herein, we map … Read more

Cancer Immunol Res. 2025 Mar 11. doi: 10.1158/2326-6066.CIR-24-0379. Online ahead of print. ABSTRACT Immune checkpoint blockade (ICB) has revolutionized the therapeutic landscape across various cancer types. However, the emergence of resistance to ICB therapy limits its clinical application. Therefore, it is necessary to better understand immune-resistance mechanisms that could be targeted by actionable drugs, and … Read more

Cancer Immunol Res. 2025 Mar 11. doi: 10.1158/2326-6066.CIR-24-0804. Online ahead of print. ABSTRACT mRNA vaccines are recognized as potent tools for immunization against viral diseases and cancer. However, the lack of a vaccine adjuvant limits the efficacy of these treatments. Here, we used cGAS mRNA, which encodes the DNA innate immune sensor, complexed with lipid … Read more

Cancer Immunol Res. 2025 Mar 11. doi: 10.1158/2326-6066.CIR-24-0263. Online ahead of print. ABSTRACT Cytotoxic chemotherapy that kills cancer cells can also elicit anti-tumor immune responses. Therefore, understanding the immunogenic context of cytotoxic chemotherapy can improve combination immunotherapies. In this study, we sought to improve our understanding about dendritic cell (DC) dynamics in cytotoxic chemotherapy-treated tumor … Read more

Cancer Immunol Res. 2025 Mar 4;13(3):309. doi: 10.1158/2326-6066.CIR-13-3-WWR. NO ABSTRACT PMID:40033981 | DOI:10.1158/2326-6066.CIR-13-3-WWR

Cancer Immunol Res. 2025 Feb 26. doi: 10.1158/2326-6066.CIR-24-1094. Online ahead of print. ABSTRACT Denosumab, a RANKL inhibitor, is primarily used to prevent osteoclastogenesis in the treatment of conditions such as osteoporosis, bone metastasis, and giant cell tumour of bone (GCTB). RANKL also plays an important role in immunity by activating NF-κB and its target genes, … Read more

Cancer Immunol Res. 2025 Feb 25:OF1-OF7. doi: 10.1158/2326-6066.CIR-24-1046. Online ahead of print. ABSTRACT The advent of syngeneic mouse tumor models provided the scientific foundation for cancer immunotherapies now in widespread use. However, in many respects, these models do not faithfully recapitulate the interactions between cancer cells and the immune systems of human patients who have … Read more

Cancer Immunol Res. 2025 Feb 21. doi: 10.1158/2326-6066.CIR-24-0591. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for many cancers but have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source … Read more

Cancer Immunol Res. 2025 Feb 12. doi: 10.1158/2326-6066.CIR-24-0335. Online ahead of print. ABSTRACT Traditional anti-cancer therapies induce tumor cell death and subsequent release of Damage Associated Molecular Patterns (DAMPs) that activate the innate inflammatory response. Paradoxically, after treatment, macrophages often adopt a pro-wound healing, rather than pro-inflammatory, phenotype and contribute to cancer progression. We found … Read more

Cancer Immunol Res. 2025 Feb 11. doi: 10.1158/2326-6066.CIR-24-0513. Online ahead of print. ABSTRACT Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system. Patients who have ovarian tumors infiltrated with high frequencies of T cells are associated with a greater survival probability. However, therapies to revitalize tumor-associated T cells, such … Read more

Cancer Immunol Res. 2025 Feb 7. doi: 10.1158/2326-6066.CIR-24-0103. Online ahead of print. ABSTRACT The tumor microenvironment (TME) in solid tumors contains myeloid cells that modulate local immune activity. STING signaling activation in these myeloid cells enhances local type I interferon (IFN) production, inducing an innate immune response that mobilizes adaptive immunity and reprograms immunosuppressive myeloid … Read more

Cancer Immunol Res. 2025 Feb 3;13(2):161. doi: 10.1158/2326-6066.CIR-13-2-WWR. NO ABSTRACT PMID:39895312 | DOI:10.1158/2326-6066.CIR-13-2-WWR

Cancer Immunol Res. 2025 Jan 31. doi: 10.1158/2326-6066.CIR-24-0979. Online ahead of print. ABSTRACT Cervical tumors are usually treated using surgery, chemotherapy, and radiotherapy, and would benefit from immunotherapies. However, the immune microenvironment in cervical cancer remains poorly described. Tertiary lymphoid structures (TLS) were recently described as markers for better immunotherapy response and overall better prognosis … Read more

Cancer Immunol Res. 2025 Jan 29. doi: 10.1158/2326-6066.CIR-23-0903. Online ahead of print. ABSTRACT Radio-immunotherapy has antitumor activity but also causes toxicity, which limits its clinical application. JS-201 is a dual antibody targeting PD-1 and TGF-β signaling. We investigated the antitumour effect of JS-201 combined with radiotherapy and the effect on radiation-induced lung injury (RILI). Different … Read more

Cancer Immunol Res. 2025 Jan 24. doi: 10.1158/2326-6066.CIR-24-0649. Online ahead of print. ABSTRACT Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples … Read more

Cancer Immunol Res. 2025 Jan 16. doi: 10.1158/2326-6066.CIR-24-0259. Online ahead of print. ABSTRACT Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide … Read more

Cancer Immunol Res. 2025 Jan 14. doi: 10.1158/2326-6066.CIR-23-0999. Online ahead of print. ABSTRACT Based on the notion that hypomorphic germline genetic variants are linked to autoimmune diseases, we reasoned that novel targets for cancer immunotherapy might be identified through germline variants associated with greater T-cell infiltration into tumors. Here, we report that while investigating germline … Read more

Cancer Immunol Res. 2025 Jan 13. doi: 10.1158/2326-6066.CIR-24-1003. Online ahead of print. ABSTRACT Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin … Read more

Cancer Immunol Res. 2025 Jan 9. doi: 10.1158/2326-6066.CIR-24-0857. Online ahead of print. ABSTRACT T cell-based therapies, including Tumor Infiltrating Lymphocyte Therapy (TIL), T cell receptor engineered T cells (TCR T), and Chimeric Antigen Receptor T cells (CAR T), are powerful therapeutic approaches for cancer treatment. While these therapies are primarily known for their direct cytotoxic … Read more

Cancer Immunol Res. 2025 Jan 9. doi: 10.1158/2326-6066.CIR-23-0563. Online ahead of print. ABSTRACT The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to … Read more

Cancer Immunol Res. 2025 Jan 9:OF1-OF19. doi: 10.1158/2326-6066.CIR-23-1011. Online ahead of print. ABSTRACT Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model … Read more

Cancer Immunol Res. 2025 Jan 9;13(1):7. doi: 10.1158/2326-6066.CIR-13-1-WWR. NO ABSTRACT PMID:39780660 | DOI:10.1158/2326-6066.CIR-13-1-WWR

Cancer Immunol Res. 2025 Jan 7. doi: 10.1158/2326-6066.CIR-24-0775. Online ahead of print. ABSTRACT Interleukin-12 (IL-12) is a potent NK cell-stimulating cytokine, but the presence of immunosuppressive myeloid cells such as myeloid-derived suppressor cells (MDSC) can inhibit IL 12-induced NK-cell cytotoxicity. Thus, we hypothesized that trabectedin, a myeloid cell-depleting agent, would improve the efficacy of IL-12 … Read more

Cancer Immunol Res. 2025 Jan 7. doi: 10.1158/2326-6066.CIR-24-0421. Online ahead of print. ABSTRACT Dendritic cells (DCs) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The rare cDC1 population is of particular interest because of its remarkable ability to cross-present antigens (Ag) to CD8+ T … Read more

Cancer Immunol Res. 2025 Jan 7. doi: 10.1158/2326-6066.CIR-24-0445. Online ahead of print. ABSTRACT Anaplastic lymphoma kinase (ALK)-fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. While ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about ALK-specific CD4+ T … Read more

Cancer Immunol Res. 2025 Jan 6:OF1-OF19. doi: 10.1158/2326-6066.CIR-24-0298. Online ahead of print. ABSTRACT Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation … Read more

Cancer Immunol Res. 2025 Jan 2. doi: 10.1158/2326-6066.CIR-24-0589. Online ahead of print. ABSTRACT Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. … Read more

Cancer Immunol Res. 2025 Jan 2. doi: 10.1158/2326-6066.CIR-24-0184. Online ahead of print. ABSTRACT Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating “cold” tumors. However, … Read more

Cancer Immunol Res. 2024 Dec 23. doi: 10.1158/2326-6066.CIR-24-0235. Online ahead of print. ABSTRACT CD8+ T-cell abundance is insufficient to assess antitumor immunity and shows poor performance in predicting breast cancer prognosis and immunotherapy response, presumably owing to the complexity of CD8+ T-cell functionalities. While single-cell RNA sequencing (scRNA-seq) can dissect the multifaceted functions of CD8+ … Read more