Cancer Immunology Research

Cancer Immunol Res. 2026 Mar 4. doi: 10.1158/2326-6066.CIR-25-0950. Online ahead of print. ABSTRACT Merkel cell carcinomas (MCC) typically arise from clonal integration of the Merkel cell polyomavirus. Immunogenic viral oncoproteins then lead to tumorigenesis. Oncoprotein-specific T cells are essential for anti-MCC immunity, but it is unclear whether B cells promote tumor control. Here, we analyzed … Read more

Cancer Immunol Res. 2026 Mar 4;14(3):373. doi: 10.1158/2326-6066.CIR-14-3-WWR. NO ABSTRACT PMID:41777151 | DOI:10.1158/2326-6066.CIR-14-3-WWR

Cancer Immunol Res. 2026 Feb 27. doi: 10.1158/2326-6066.CIR-25-0611. Online ahead of print. ABSTRACT Providing cytokine signaling is a key strategy to boost the efficacy of chimeric antigen receptor (CAR) T cell therapy. However, the individual roles of key downstream mediators, STAT3 and STAT5, remain incompletely understood. In this study, we engineered CAR T cells to … Read more

Cancer Immunol Res. 2026 Feb 27. doi: 10.1158/2326-6066.CIR-25-1229. Online ahead of print. ABSTRACT Natural killer (NK) cells represent key effectors of antitumor immunity, yet emerging evidence highlights populations with distinct roles in cancer. Despite such expanded diversity within the NK cell repertoire, we lack an understanding of how this heterogeneity impacts immune responses and downstream … Read more

Cancer Immunol Res. 2026 Feb 25. doi: 10.1158/2326-6066.CIR-25-1060. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICI), including those that block PD-1/PD-L1, have revolutionized therapy for patients with non-small cell lung cancer. However, most patients demonstrate no clinical benefit or acquire resistance, even when tumors express PD-L1. This highlights the critical need to dissect tumor … Read more

Cancer Immunol Res. 2026 Feb 25. doi: 10.1158/2326-6066.CIR-25-0758. Online ahead of print. ABSTRACT The existence of intra-tumoral tertiary lymphoid structures (TLSs) has been reported to be correlated with reduced recurrence of hepatocellular carcinoma (HCC). However, the cellular characteristics and driving mechanism of TLSs in HCC remain largely unknown. In this study, we compared clinical outcomes … Read more

Cancer Immunol Res. 2026 Feb 25. doi: 10.1158/2326-6066.CIR-25-0836. Online ahead of print. ABSTRACT Immunotherapies have revolutionized the treatment of hepatocellular carcinoma (HCC), yet their response rates remain limited, highlighting the need for new therapeutic targets. In this study, we found that VSIG4 (V-set and immunoglobulin domain containing 4) is predominantly expressed by macrophages in both … Read more

Cancer Immunol Res. 2026 Feb 24. doi: 10.1158/2326-6066.CIR-25-1381. Online ahead of print. ABSTRACT Anti-CD19 chimeric antigen receptor (CAR) therapy demonstrated remarkable efficacy against hematological malignancies. However, B cell malignancies with lymph node (LN) involvement frequently remain resistant. Here, we show that CAR T cells downregulated the chemokine receptor CCR7, crucial for nodal homing, during manufacturing. … Read more

Cancer Immunol Res. 2026 Feb 20. doi: 10.1158/2326-6066.CIR-25-0243. Online ahead of print. ABSTRACT Microsatellite-stable metastatic colorectal cancer (MSS mCRC) remains resistant to conventional immunotherapies. In a phase I trial, we observed encouraging efficacy of the combination of regorafenib, ipilimumab, and nivolumab (RIN), with a 27.6% overall response rate and a median overall survival of 20 … Read more

Cancer Immunol Res. 2026 Feb 20. doi: 10.1158/2326-6066.CIR-25-1016. Online ahead of print. ABSTRACT Autologous tumor-infiltrating lymphocyte (TIL) cell therapy is showing promising efficacy against immunologically “hot” tumors such as melanoma, cervical cancer, and renal cancer. However, generation of tumoricidal TIL from cold tumors with a low tumor mutational burden, such as many sarcoma types, poses … Read more

Cancer Immunol Res. 2026 Feb 13. doi: 10.1158/2326-6066.CIR-25-0766. Online ahead of print. ABSTRACT Colorectal cancer (CRC) is a highly heterogeneous malignancy characterized by complex interactions between tumor cells and the immune system. The tumor microenvironment (TME) plays a crucial role in CRC progression and response to therapy. However, the mechanisms regulating TME composition remain poorly … Read more

Cancer Immunol Res. 2026 Feb 13. doi: 10.1158/2326-6066.CIR-25-0798. Online ahead of print. ABSTRACT Tumor infiltrating lymphocytes (TILs) can be isolated from patient tumors, greatly expanded ex vivo, and returned to the patient for therapeutic effect. Recent clinical trials have highlighted the efficacy of TILs for a subset of patients and supported FDA approval for melanoma. … Read more

Cancer Immunol Res. 2026 Feb 13. doi: 10.1158/2326-6066.CIR-25-0663. Online ahead of print. ABSTRACT Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts (CAFs), is a promising therapeutic target to achieve normalization of the tumor microenvironment. We previously established an ex vivo retroviral-transduced FAP-specific chimeric antigen receptor (FAP-CAR) T-cell approach to deplete FAP+ CAFs … Read more

Cancer Immunol Res. 2026 Feb 13. doi: 10.1158/2326-6066.CIR-25-0635. Online ahead of print. ABSTRACT Tumor-infiltrating B lymphocytes (TIL-Bs) are increasingly recognized as favorable prognostic markers in multiple cancer types and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic … Read more

Cancer Immunol Res. 2026 Feb 13:OF1-OF16. doi: 10.1158/2326-6066.CIR-25-0558. Online ahead of print. ABSTRACT High-dose interleukin 2 (HD IL2) produces durable responses in patients with advanced cancer, but its use is limited by life-threatening toxicities such as vascular leak syndrome (VLS). To improve the therapeutic index for IL2, a class of IL2 molecules has been engineered … Read more

Cancer Immunol Res. 2026 Feb 11. doi: 10.1158/2326-6066.CIR-25-0431. Online ahead of print. ABSTRACT Bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma, have distinct molecular subtypes. The proliferative subtype, enriched with bronchial dysplasia, had decreased expression of an antigen processing/presentation gene co-expression module in progressive/persistent versus regressive PMLs, suggesting a functional impact of these … Read more

Cancer Immunol Res. 2026 Feb 10. doi: 10.1158/2326-6066.CIR-25-0979. Online ahead of print. ABSTRACT Anti-PD1 therapies improve survival in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), but only a minority of patients achieve durable responses. The mechanisms driving resistance to anti-PD1 in SCCHN remain poorly understood. Using the IMMUcan multi-omics workflow, we … Read more

Cancer Immunol Res. 2026 Feb 6. doi: 10.1158/2326-6066.CIR-25-0666. Online ahead of print. ABSTRACT Tumor-associated antigen (TAA) vaccines are being explored as a strategy to induce antitumor immune responses. Mammaglobin-A (Mam-A) is a TAA expressed in >50% of breast cancer (BC) patients. Previously, we have shown that Mam-A DNA vaccines induce antitumor immune responses in patients … Read more

Cancer Immunol Res. 2026 Feb 4. doi: 10.1158/2326-6066.CIR-25-0693. Online ahead of print. ABSTRACT Some patients undergoing immune checkpoint blockade treatment develop immune-related adverse events (irAEs) affecting multiple organs, but whether pituitary and thyroid dysfunction are prone to co-occur is unclear. A total of 1,014 patients treated at Nagoya University Hospital were prospectively assessed for pituitary … Read more

Cancer Immunol Res. 2026 Feb 3;14(2):181. doi: 10.1158/2326-6066.CIR-14-2-WWR. NO ABSTRACT PMID:41630580 | DOI:10.1158/2326-6066.CIR-14-2-WWR

Cancer Immunol Res. 2026 Jan 30. doi: 10.1158/2326-6066.CIR-25-0646. Online ahead of print. ABSTRACT The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is predominantly shaped by tumor-associated macrophages (TAMs), yet the key chemokine axes driving immunosuppression and progression remain poorly defined. In this study, we identified the CCL1-AMFR axis as a critical contributor to GBM progression … Read more

Cancer Immunol Res. 2026 Jan 23. doi: 10.1158/2326-6066.CIR-25-0844. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with liver metastases significantly worsening outcomes. However, features of the tumor microenvironment (TME) that are distinct between primary and metastatic sites remain poorly defined. Cellular neighborhoods within the TME are recognized as functional … Read more

Cancer Immunol Res. 2026 Jan 27:OF1-OF13. doi: 10.1158/2326-6066.CIR-25-0256. Online ahead of print. ABSTRACT Subcutaneous administration is an increasingly patient-preferred, alternative route of administration for monoclonal antibodies (mAb). To overcome the dose-volume restriction with subcutaneous administration and enable the large mAb doses typically required for immunotherapy, recombinant human hyaluronidase PH20 is co-dosed to transiently depolymerize hyaluronan … Read more

Cancer Immunol Res. 2026 Jan 21. doi: 10.1158/2326-6066.CIR-25-0567. Online ahead of print. ABSTRACT Lung cancer is the leading cause of cancer-related deaths worldwide and, despite advances in treatment, immune suppression remains an obstacle to effective therapy. Effector CD4+ T cells (CD4+ Teffs) are critical for antitumor immunity, but their function is often inhibited by regulatory … Read more

Cancer Immunol Res. 2026 Jan 21. doi: 10.1158/2326-6066.CIR-25-0743. Online ahead of print. ABSTRACT Identifying new therapeutic approaches in high-grade serous ovarian cancer (HGSC) requires the development of more accurate preclinical models that replicate the patient-specific tumor and its microenvironment. To address this, we established immunocompetent patient-derived cultures (iPDCs) for HGSC, cultured on a physiologically relevant … Read more

Cancer Immunol Res. 2026 Jan 21. doi: 10.1158/2326-6066.CIR-24-0527. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a non-enriched product, thereby improving duration of response (DOR). We conducted a phase 1 study with bb21217 (NCT03274219), an anti-B-cell maturation antigen CAR T-cell therapy … Read more

Cancer Immunol Res. 2026 Jan 20. doi: 10.1158/2326-6066.CIR-25-0695. Online ahead of print. ABSTRACT GPR84 is a medium-chain free fatty acid receptor predominantly expressed in myeloid cells. Previous studies have identified GPR84 as an enhancer of the pro-inflammatory myeloid cell responses and a regulator of metabolic homeostasis. However, the role of GPR84 in T cell function … Read more

Cancer Immunol Res. 2026 Jan 15. doi: 10.1158/2326-6066.CIR-24-1159. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) represent the main immune population infiltrating cancers, and their abundance is generally correlated with a poor prognosis. The acquisition of protumor properties by TAMs involves several mechanisms, including expression of immunosuppressive enzymes. In this study, we explored the role … Read more

Cancer Immunol Res. 2026 Jan 14:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-1596. Online ahead of print. ABSTRACT Oncolytic viruses (OV) are thought to mediate antitumor activity by killing tumor cells and inducing antitumor immunity, but how this happens is not well understood. In this issue, Ludwig and colleagues show that PVSRIPO, an oncolytic poliovirus being developed for glioblastoma, may … Read more

Cancer Immunol Res. 2026 Jan 13:OF1-OF2. doi: 10.1158/2326-6066.CIR-25-1344. Online ahead of print. ABSTRACT Adoptive T-cell therapies have shown limited efficacy against solid tumors, so new approaches are required. In this issue, Chantzoura and colleagues describe MiNK-215, a novel allogeneic fibroblast activation protein-targeting chimeric antigen receptor invariant NK T-cell therapy engineered to secrete IL15. They show … Read more

Cancer Immunol Res. 2026 Jan 12. doi: 10.1158/2326-6066.CIR-25-1126. Online ahead of print. ABSTRACT Combination vaccine and checkpoint inhibitor therapy has previously demonstrated immunologic responses in patients with pancreatic ductal adenocarcinoma (PDAC), although with limited efficacy. An urgent need to augment responses has warranted a deeper understanding of how each treatment modality contributes to the overall … Read more

Cancer Immunol Res. 2026 Jan 12. doi: 10.1158/2326-6066.CIR-25-0545. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal and has poor immunogenicity, warranting the use of vaccines to guide and recruit the immune response. Building on prior efforts to achieve clinical immunotherapeutic responses against PDAC, we conducted a phase II study (NCT03190265) that … Read more

Cancer Immunol Res. 2026 Jan 12:OF1-OF8. doi: 10.1158/2326-6066.CIR-25-1479. Online ahead of print. ABSTRACT The transition from trainee to independent investigator is one of the most challenging and formative phases of a scientific career. It requires not only scientific expertise but also the skills to lead, mentor, manage, and communicate effectively. The Arthur and Sandra Irving … Read more

Cancer Immunol Res. 2026 Jan 9. doi: 10.1158/2326-6066.CIR-25-0873. Online ahead of print. ABSTRACT Pseudomonas aeruginosa infection is still a serious problem among immunocompromised patients who have advanced urinary tract malignancies, yet the impact of P. aeruginosa on disease progression remains poorly defined. Here, we show that urinary tract infections (UTI) caused by P. aeruginosa exacerbated … Read more

Cancer Immunol Res. 2026 Jan 9:OF1-OF11. doi: 10.1158/2326-6066.CIR-25-1018. Online ahead of print. ABSTRACT The gut microbiome has emerged as a modulator of both cancer progression and patient responses to therapies like immune checkpoint inhibitors (ICI). Recent evidence highlights microbially derived metabolites as key regulators of immune response and tumor microenvironment dynamics. This review explores the … Read more

Cancer Immunol Res. 2026 Jan 8. doi: 10.1158/2326-6066.CIR-25-0880. Online ahead of print. ABSTRACT The ability of interleukin-12 (IL-12) to stimulate production of interferon gamma (IFN-γ) suggested it might improve the efficacy of low dose interferon alpha (IFN-α). In this phase II trial, patients with metastatic malignant melanoma were administered recombinant human (rh) IL-12 followed by … Read more

Cancer Immunol Res. 2026 Jan 8;14(1):7. doi: 10.1158/2326-6066.CIR-14-1-WWR. NO ABSTRACT PMID:41502309 | DOI:10.1158/2326-6066.CIR-14-1-WWR

Cancer Immunol Res. 2026 Jan 8;14(1):8-9. doi: 10.1158/2326-6066.CIR-25-1391. NO ABSTRACT PMID:41502310 | DOI:10.1158/2326-6066.CIR-25-1391

Cancer Immunol Res. 2026 Jan 7. doi: 10.1158/2326-6066.CIR-25-0834. Online ahead of print. ABSTRACT While the role of neutrophils in modulating antitumor T cell responses has been extensively studied, their direct effects on tumor cells remains less well understood. In this study, we investigated whether neutrophils have the capacity to directly kill tumor cells independently of … Read more

Cancer Immunol Res. 2025 Dec 29. doi: 10.1158/2326-6066.CIR-25-0583. Online ahead of print. ABSTRACT Relapsed and refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) presents a significant challenge in hematology-oncology, with approximately 30-40% of DLBCL patients experiencing relapse or resistance to treatment. This underscores the urgent need to better understand the molecular mechanisms governing therapeutic resistance. Signal Transducer … Read more

Cancer Immunol Res. 2025 Dec 9. doi: 10.1158/2326-6066.CIR-25-0242. Online ahead of print. ABSTRACT Tumor cells employ metabolic mechanisms to limit antitumor immunity and promote resistance to immunotherapy. However, how immunotherapy modulates tumor metabolism remains unclear. Here, we demonstrated that anti-PD-1 treatment regulated cholesterol biosynthesis in cancer cells through the effector cytokine interferon IFN-γ. Mechanistically, IFN-γ-induced … Read more

Cancer Immunol Res. 2025 Dec 8. doi: 10.1158/2326-6066.CIR-25-0070. Online ahead of print. ABSTRACT Vaccines that encode tumour-associated antigens are potent boosting agents for adoptively transferred tumour-specific T cells. Employing vaccines to boost adoptively transferred tumour-reactive T cells relies on a priori knowledge of tumour epitopes, isolation of matched epitope-specific T cells, and personalized vaccines, all … Read more

Cancer Immunol Res. 2025 Dec 5. doi: 10.1158/2326-6066.CIR-25-0514. Online ahead of print. ABSTRACT Adoptive transfer of T lymphocytes specific for tumor-associated neoantigens can elicit immunity against solid tumors in patients. However, how these antigens impact T cell function, effector differentiation, and persistence remains unclear. We examined how an identical CD8+ T cell product was shaped … Read more

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