Cancer Immunology Research

Cancer Immunol Res. 2025 Dec 2;13(12):1893. doi: 10.1158/2326-6066.CIR-13-12-WWR. NO ABSTRACT PMID:41327976 | DOI:10.1158/2326-6066.CIR-13-12-WWR

Cancer Immunol Res. 2025 Dec 1:OF1-OF12. doi: 10.1158/2326-6066.CIR-25-0631. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of cancer. However, the durable response to this therapy remains low, and there is a risk of moderate-to-severe toxicities following treatment that requires close monitoring. Over the past decade, we have learned … Read more

Cancer Immunol Res. 2025 Nov 26. doi: 10.1158/2326-6066.CIR-25-0444. Online ahead of print. ABSTRACT Treatment of melanoma with BRAF inhibitors plus MEK inhibitors (BRAFi + MEKi) stimulates an intratumoral immune response, in part through pyroptosis mediated by the pore-forming protein gasdermin E (GSDME/Gsdme). How GSDME mediates effects on tumoral immunity is not well characterized. Using single-cell … Read more

Cancer Immunol Res. 2025 Nov 21. doi: 10.1158/2326-6066.CIR-25-0756. Online ahead of print. ABSTRACT Tumor-draining lymph nodes are a pivotal site for antitumor T-cell priming. However, their mechanistic roles in cancer immune surveillance and immunotherapy response remain poorly defined. Intratumor (IT) virotherapy generates antitumor T-cell immunity through multifaceted engagement of innate antiviral inflammation. Here we identify … Read more

Cancer Immunol Res. 2025 Nov 21. doi: 10.1158/2326-6066.CIR-25-0168. Online ahead of print. ABSTRACT Large parallel genetic screens have been used to identified targets and regulators that enhance T cell antitumor capability and persistence in tumor microenvironment. We hypothesized that by combining the pooled screen data from multiple independent genetic screens we could provide a systematic, … Read more

Cancer Immunol Res. 2025 Nov 21. doi: 10.1158/2326-6066.CIR-25-0445. Online ahead of print. ABSTRACT Tissue-resident memory T (TRM) cells, memory T cells that stably occupy tissues and contribute to immunosurveillance, induce favorable survival outcomes in solid tumors. While TRM cells have been observed in lymph nodes, their phenotype and prognostic significance in diffuse large B-cell lymphoma … Read more

Cancer Immunol Res. 2025 Nov 18. doi: 10.1158/2326-6066.CIR-25-0625. Online ahead of print. ABSTRACT The activity of bispecific antibodies against vascular endothelial growth factor (VEGF) and programmed death ligand-1 (PD-1) have reinvigorated interest in dual VEGF and PD-1 targeting across solid tumors. However, the tumor and immune features influencing tumor response remain largely unknown. We conducted … Read more

Cancer Immunol Res. 2025 Nov 14. doi: 10.1158/2326-6066.CIR-25-0454. Online ahead of print. ABSTRACT Invariant Natural Killer T (iNKT) cells are a conserved T lymphocyte population capable of acting on dendritic cells (DCs) to potently amplify downstream immune responses. However, the processes underlying such iNKT adjuvancy remain poorly understood. Here, we showed that allogeneic human CD4+ … Read more

Cancer Immunol Res. 2025 Nov 14. doi: 10.1158/2326-6066.CIR-25-0349. Online ahead of print. ABSTRACT Cellular immunotherapies show remarkable efficacy against hematological malignancies. However, applying these therapies against solid tumors is challenging. Among the obstacles are the lack of tumor-specific antigens and the immunosuppressive tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) are key … Read more

Cancer Immunol Res. 2025 Nov 13. doi: 10.1158/2326-6066.CIR-24-1255. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) play crucial and important role in cancer dynamics by affecting homeostasis, immunosuppression, and angiogenesis within the tumor microenvironment. Using single-cell transcriptomics, we constructed a comprehensive atlas of myeloid cell populations across healthy and pan-cancer tissues that revealed heterogeneity. Our … Read more

Cancer Immunol Res. 2025 Nov 12. doi: 10.1158/2326-6066.CIR-25-0481. Online ahead of print. ABSTRACT The immune microenvironment is a crucial component of colorectal carcinoma (CRC) that has been well characterized, but much less is known about the immune microenvironment of CRC precursors. We hypothesized that T-cell infiltrates might differ across the colorectal neoplastic spectrum. We leveraged … Read more

Cancer Immunol Res. 2025 Nov 11. doi: 10.1158/2326-6066.CIR-25-0310. Online ahead of print. ABSTRACT Despite advances in immune checkpoint blockade (ICB) for cancer treatment, only a minority of triple-negative breast cancer (TNBC) patients derive benefits, and the underlying mechanisms remain largely unknown. Herein, sequence similarity 135 family member B (FAM135B) is identified as a regulator of … Read more

Cancer Immunol Res. 2025 Nov 7. doi: 10.1158/2326-6066.CIR-25-0062. Online ahead of print. ABSTRACT Effective antitumor immunity ultimately depends on the priming and activation of tumor-specific cytotoxic CD8+ T cells; however, the role of intratumoral cell-cell immune interactions remains incompletely understood. Recent work has revealed that the temporospatial colocalization of dendritic cells (DCs), helper T cells … Read more

Cancer Immunol Res. 2025 Nov 7:OF1-OF17. doi: 10.1158/2326-6066.CIR-25-0438. Online ahead of print. ABSTRACT Endometrial cancer is the sixth most common cancer in women worldwide and the fourth most common cancer in women in the United States. In the United States, its incidence and mortality rates have continued to increase since the late 1990s. Endometrial cancer … Read more

Cancer Immunol Res. 2025 Nov 4. doi: 10.1158/2326-6066.CIR-25-0744. Online ahead of print. ABSTRACT Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. Here, we demonstrate that RMC-7977, a preclinical RAS(ON) multi-selective inhibitor representative of the investigational agent daraxonrasib (RMC-6236), was able to elicit potent antitumor immune responses across multiple NRAS-mutant melanoma models. Treatment with … Read more

Cancer Immunol Res. 2025 Nov 3;13(11):1696-1697. doi: 10.1158/2326-6066.CIR-25-1175. NO ABSTRACT PMID:41178332 | DOI:10.1158/2326-6066.CIR-25-1175

Cancer Immunol Res. 2025 Nov 3;13(11):1695. doi: 10.1158/2326-6066.CIR-13-11-WWR. NO ABSTRACT PMID:41178331 | DOI:10.1158/2326-6066.CIR-13-11-WWR

Cancer Immunol Res. 2025 Oct 29. doi: 10.1158/2326-6066.CIR-25-0677. Online ahead of print. ABSTRACT Patients with Sezary syndrome (SS), the aggressive leukemic variant of cutaneous T cell lymphoma (CTCL), have few therapeutic options and a poor prognosis. We previously showed that the IL4/IL13 signaling pathway impacts SS tumorigenesis. Here, we investigated the potential therapeutic effect of … Read more

Cancer Immunol Res. 2025 Oct 27. doi: 10.1158/2326-6066.CIR-25-0594. Online ahead of print. ABSTRACT Human leukocyte antigen class I (HLA-I) is central to tumor immune recognition, but its regulatory mechanisms in cervical cancer remain poorly understood. This study aimed to elucidate the impact of HLA-I regulatory mechanisms on CD8+ T cell infiltration and identify distinct histotype-specific … Read more

Cancer Immunol Res. 2025 Oct 27. doi: 10.1158/2326-6066.CIR-25-0190. Online ahead of print. ABSTRACT Thymomas are rare thymic epithelial tumors harboring a high but variable proportion of lymphocytes without obvious function. Autoimmunity is present in one third of patients at diagnosis. Herein, we performed a phenotypic, single-cell RNA sequencing (scRNAseq), and spatial analysis of both the … Read more

Cancer Immunol Res. 2025 Oct 23. doi: 10.1158/2326-6066.CIR-25-0082. Online ahead of print. ABSTRACT Tumor-specific CD8+ T cells in blood appear to be important for and predictive of response to anti-PD-1 therapies. However, as most tumor antigens are unique to a given patient, identification of tumor-specific CD8+ T cells is not routinely feasible. Here, we characterized … Read more

Cancer Immunol Res. 2025 Oct 20. doi: 10.1158/2326-6066.CIR-24-0207. Online ahead of print. ABSTRACT Aberrant expression of the oncogene SALL4 is associated with stemness, more aggressive cancer phenotype, and reduced patient survival in various tumor types making SALL4 a potential target for cancer immunotherapy. We conducted a transcriptional analysis of SALL4 expression in colorectal cancer (CRC) … Read more

Cancer Immunol Res. 2025 Oct 20. doi: 10.1158/2326-6066.CIR-25-0433. Online ahead of print. ABSTRACT Immune checkpoint blockade (ICB) has transformed colorectal cancers (CRCs) therapy, yet the majority of microsatellite-stable (MSS) CRCs remain refractory due to insufficient tumor-immune cell crosstalk. Identifying molecular regulators that modulate the tumor immune microenvironment (TIME) is crucial for expanding ICB efficacy. Here, … Read more

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