Cancer Immunology Research

Cancer Immunol Res. 2025 Oct 13. doi: 10.1158/2326-6066.CIR-25-0203. Online ahead of print. ABSTRACT Neoantigen-specific T cells recognize tumor cells and are critical for cancer immunotherapies to be effective. However, the transcriptional program controlling the cell-fate decisions by neoantigen-specific T cells is incompletely understood. Here, using joint single-cell transcriptome and T-cell receptor (TCR) profiling, we mapped … Read more

Cancer Immunol Res. 2025 Oct 13. doi: 10.1158/2326-6066.CIR-24-1259. Online ahead of print. ABSTRACT Natural killer (NK) cells play a critical role in anti-cancer immunity through their direct cytotoxicity and production of cytokines, such as Flt3L. NK cell production of Flt3L controls conventional type I dendritic cell (cDC1) abundance in the tumor and promotes protective immune … Read more

Cancer Immunol Res. 2025 Oct 8:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-1097. Online ahead of print. ABSTRACT Overcoming the physical barriers of the tumor microenvironment remains a major obstacle for chimeric antigen receptor (CAR) T-cell therapy in solid tumors. In this issue, Van Pelt and colleagues show that engineering GD2-targeting CAR T cells to express matrix metalloproteinase 7 and … Read more

Cancer Immunol Res. 2025 Oct 1. doi: 10.1158/2326-6066.CIR-25-0343. Online ahead of print. ABSTRACT Immune check-point blockade for the treatment of malignancies has been focused on reversing inhibitory pathways in T lymphocytes. Natural killer (NK) cells are a potent innate defense against tumors and virally infected cells, but their therapeutic manipulation for anti-cancer immunity has been … Read more

Cancer Immunol Res. 2025 Oct 1;13(10):1509. doi: 10.1158/2326-6066.CIR-13-10-WWR. NO ABSTRACT PMID:41030051 | DOI:10.1158/2326-6066.CIR-13-10-WWR

Cancer Immunol Res. 2025 Sep 30. doi: 10.1158/2326-6066.CIR-24-1342. Online ahead of print. ABSTRACT Low or absent expression of major histocompatibility complex (MHC) on tumor cells is a presumed mechanism of resistance to immunotherapy, but evidence for this has largely been indirect. Likewise, whether immunotherapy can be effective without tumor MHC expression is also poorly understood. … Read more

Cancer Immunol Res. 2025 Sep 26. doi: 10.1158/2326-6066.CIR-25-0182. Online ahead of print. ABSTRACT Current histopathological classifications do not reliably distinguish patients with primary cutaneous squamous cell carcinoma (cSCC) at risk of relapse from those with non-relapsing tumors. This underscores the need for molecular signatures capable of stratifying patients during primary tumor resection. Here, we used … Read more

Cancer Immunol Res. 2025 Sep 26. doi: 10.1158/2326-6066.CIR-24-1083. Online ahead of print. ABSTRACT Despite advances in cancer immunotherapy, treatment response is still highly variable. One contributing factor is the tumor microenvironment and specifically the presence of suppressive immune cells such as regulatory T (Treg) cells. Being able to target these specifically, whilst leaving effector T … Read more

Cancer Immunol Res. 2025 Sep 19. doi: 10.1158/2326-6066.CIR-25-0535. Online ahead of print. ABSTRACT Reinvigoration of tumor-reactive T cells using co-stimulatory bispecific antibodies (bsAbs) targeting CD28 is emerging as a promising therapeutic strategy. Conditional, tumor-specific recruitment can offer a layer of control and specificity. We developed pH-selective CD28xVISTA bsAbs to act specifically within the acidic tumor … Read more

Cancer Immunol Res. 2025 Sep 18. doi: 10.1158/2326-6066.CIR-24-1011. Online ahead of print. ABSTRACT The immunosuppressive tumor microenvironment (TME) remains a major barrier to effective immunotherapy in gastric cancer (GC). Here, we identified the E3 ubiquitin ligase BFAR as a critical regulator of neutrophil-mediated immune evasion through the S100A8/A9-BFAR-PRP19-YBX1 signaling axis. Multi-omics analyses revealed that BFAR … Read more

Cancer Immunol Res. 2025 Sep 10. doi: 10.1158/2326-6066.CIR-25-0075. Online ahead of print. ABSTRACT Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. … Read more

Cancer Immunol Res. 2025 Sep 9. doi: 10.1158/2326-6066.CIR-25-0174. Online ahead of print. ABSTRACT Natural killer (NK) cell licensing is an educational process that enhances responsiveness to activating signals in maturing NK cells and is predominantly regulated by major histocompatibility complex (MHC) class I-specific inhibitory signals. However, the role of non-MHC signalling in this process remains … Read more

Cancer Immunol Res. 2025 Sep 9. doi: 10.1158/2326-6066.CIR-24-0440. Online ahead of print. ABSTRACT Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by immunosuppressive tumor microenvironment (TME) maintained by tumor-associated macrophages (TAMs) hindering anti-tumor responses and immunotherapy efficacy. Here we show that targeting retinoblastoma protein (Rb) by disruption of … Read more

Cancer Immunol Res. 2025 Sep 8:OF1. doi: 10.1158/2326-6066.CIR-25-0804. Online ahead of print. NO ABSTRACT PMID:40920201 | DOI:10.1158/2326-6066.CIR-25-0804

Cancer Immunol Res. 2025 Sep 8. doi: 10.1158/2326-6066.CIR-25-0527. Online ahead of print. ABSTRACT Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields … Read more

Cancer Immunol Res. 2025 Sep 8. doi: 10.1158/2326-6066.CIR-25-0575. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is defined by a myeloid-enriched microenvironment and has shown remarkable resistance to immune checkpoint blockade (e.g., PD-1 and CTLA-4). Here, we sought to define the role of myeloid immunosuppression in immune resistance in PDA. We report that depletion … Read more

Cancer Immunol Res. 2025 Sep 4. doi: 10.1158/2326-6066.CIR-25-0488. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) display remarkable functional heterogeneity, yet the molecular mechanisms driving their diverse phenotypes remain elusive. Using CRISPR screens in primary macrophages, we identified tumor-derived factors, including lactic acid, PGE2, and GM-CSF, as key modulators of TAM polarization. These factors interact … Read more

Cancer Immunol Res. 2025 Sep 4. doi: 10.1158/2326-6066.CIR-24-1074. Online ahead of print. ABSTRACT Liver metastases are associated with poor cancer outcomes in many solid malignancies, but the factors influencing the trajectory of patients with liver metastases are poorly defined. It is known that liver metastases suppress systemic antitumor immunity; however, the underlying mechanisms remain incompletely … Read more

Cancer Immunol Res. 2025 Sep 4. doi: 10.1158/2326-6066.CIR-25-0086. Online ahead of print. ABSTRACT The discovery of immune checkpoints and the rapid growth of immuno-oncology (IO) have sparked efforts to utilize the immune system to treat a wide range of cancer types/subtypes. While the major focus of IO over the past decades has been to manipulate … Read more

Cancer Immunol Res. 2025 Sep 2;13(9):1325. doi: 10.1158/2326-6066.CIR-13-9-WWR. NO ABSTRACT PMID:40891195 | DOI:10.1158/2326-6066.CIR-13-9-WWR

Cancer Immunol Res. 2025 Sep 1. doi: 10.1158/2326-6066.CIR-24-1228. Online ahead of print. ABSTRACT Combination chemotherapy and immunotherapy are effective against advanced gastric cancer (GC). However, T cell exhaustion in the tumor microenvironment may decrease the immune response and compromise the effectiveness of immunotherapy. Herein, we report the potential role of EBI3 in promoting T cell … Read more

Cancer Immunol Res. 2025 Sep 1. doi: 10.1158/2326-6066.CIR-25-0149. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy against hematologic malignancies but has struggled to achieve comparable success in solid tumors. A key obstacle in solid tumors is the extracellular matrix (ECM), which impedes CAR T-cell infiltration. In clinical trials, … Read more

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-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 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 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-24-0737. 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 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 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