Cancer Immunology Research

Cancer Immunol Res. 2026 Sep 4. doi: 10.1158/2326-6066.CIR-26-0472. Online ahead of print. ABSTRACT The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by restrained function of effector T cells that drives resistance to immunotherapy. While tumor-extrinsic stroma and myeloid cells have been shown to mediate PDAC immune evasion, the role of tumor-intrinsic post-transcriptional … Read more

Cancer Immunol Res. 2026 Sep 4:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0906. Online ahead of print. ABSTRACT The therapeutic potential of chimeric antigen receptor (CAR) T cells has long been limited by the static nature of the engineered receptor; once manufactured, the cell is committed to a single antigen, unable to respond to the immune evasion and antigen heterogeneity … Read more

Cancer Immunol Res. 2026 Sep 2;14(9):1369. doi: 10.1158/2326-6066.CIR-14-9-WWR. NO ABSTRACT PMID:42682071 | DOI:10.1158/2326-6066.CIR-14-9-WWR

Cancer Immunol Res. 2026 Aug 31. doi: 10.1158/2326-6066.CIR-26-0177. Online ahead of print. ABSTRACT Immune checkpoint blockade (ICB) has markedly improved overall survival in various cancers, but is associated with severe and sometimes fatal immune-related adverse events (irAEs). Current management of irAEs involves discontinuation of ICB therapy and administration of immunosuppressive drugs, such as corticosteroids, which … Read more

Cancer Immunol Res. 2026 Aug 31. doi: 10.1158/2326-6066.CIR-25-1379. Online ahead of print. ABSTRACT The efficacy of immunotherapy in unresectable/recurrent/metastatic head and neck squamous cell carcinoma (U/R/M HNSCC) remains suboptimal compared to primary untreated resectable HNSCC. The immunological and stromal landscape during immunotherapy in U/R/M HNSCC is crucial for understanding drug resistance mechanisms. In this study, … Read more

Cancer Immunol Res. 2026 Aug 31. doi: 10.1158/2326-6066.CIR-26-0104. Online ahead of print. ABSTRACT Tertiary lymphoid structures (TLS) have emerged as critical immune niches within the tumor microenvironment across various cancers. However, their structural organization and functional roles in non-muscle-invasive bladder cancer (NMIBC) remain poorly characterized. In this study, we comprehensively characterized TLS in NMIBC using … Read more

Cancer Immunol Res. 2026 Aug 26. doi: 10.1158/2326-6066.CIR-25-1589. Online ahead of print. ABSTRACT T-cell immune tolerance is established in part through the activity of the Auto-immune Regulator (AIRE) transcription factor in the medullary thymic epithelial cells (mTEC) of the thymus. AIRE induces expression of peripheral tissue-specific self-antigens for presentation to naïve T cells to promote … Read more

Cancer Immunol Res. 2026 Aug 26. doi: 10.1158/2326-6066.CIR-25-1471. Online ahead of print. ABSTRACT Despite the availability of various treatment modalities for liver cancer, its mortality rate remains high. Immunotherapy represents an emerging approach for liver cancer. However, the response rate to single-agent immune checkpoint blockade therapy is suboptimal. Endoplasmic reticulum oxidoreductase 1-alpha (ERO1A), a potential … Read more

Cancer Immunol Res. 2026 Aug 26. doi: 10.1158/2326-6066.CIR-25-1353. Online ahead of print. ABSTRACT Head and Neck Head and Neck Squamous Cell Carcinoma (HNSCC) is driven by an immunosuppressive tumor microenvironment (TME). We examined the immune-modulatory role of EphA4 in HNSCC using spatial analysis, multi-compartment RNA-sequencing from Oral Cavity Squamous Cell Carcinoma (OCSCC), and three genetically … Read more

Cancer Immunol Res. 2026 Aug 17. doi: 10.1158/2326-6066.CIR-26-0278. Online ahead of print. ABSTRACT Triple-negative breast cancer (TNBC) has high rates of recurrence despite chemotherapy and immune checkpoint blockade (ICB). Tumor-associated macrophages (TAMs) can either suppress or support antitumor immunity, but the mechanisms governing these states and therapeutic targets remain unclear. Here, integrating public scRNAseq datasets … Read more

Cancer Immunol Res. 2026 Aug 14. doi: 10.1158/2326-6066.CIR-26-0160. Online ahead of print. ABSTRACT Occasional complete responses to immune checkpoint inhibitor therapy demonstrate that acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) can be immune-sensitive when appropriately targeted. Here, we analyzed AML/MDS patients (n=14) treated with the anti-TIM3 sabatolimab and the hypomethylating agent decitabine in a … Read more

Cancer Immunol Res. 2026 Aug 13. doi: 10.1158/2326-6066.CIR-26-0365. Online ahead of print. ABSTRACT Endogenous retrotransposable elements (EREs) can modulate immune responses. We explored ERE transcription in relation to response to immune checkpoint inhibition in advanced solid tumors. ERE expression was measured in pre and on-treatment samples from patients treated in a clinical trial with pembrolizumab. … Read more

Cancer Immunol Res. 2026 Aug 13. doi: 10.1158/2326-6066.CIR-26-0126. Online ahead of print. ABSTRACT Alterations in peripheral immunity may contribute to fatal prostate cancer and the excessive disease burden among African American (AA) men. Thus, we investigated peripheral immunity in prostate cancer patients in association with disease outcome and AA descent. We performed single-cell RNA and … Read more

Cancer Immunol Res. 2026 Aug 11. doi: 10.1158/2326-6066.CIR-25-1334. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR)-T cell exhaustion constitutes a critical barrier to sustained antitumor efficacy. Through transcriptomic analysis of CAR-T cells from patients with lymphoma, we identified the histone variant macroH2A2 (H2AFY2) as a critical regulator of T cell exhaustion-a finding consistently observed … Read more

Cancer Immunol Res. 2026 Aug 11. doi: 10.1158/2326-6066.CIR-25-1445. Online ahead of print. ABSTRACT Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy for early-stage bladder cancer (BCa), based on its immunostimulatory activity. However, over half of patients experience BCG failure and subsequent recurrence. The heterogeneity of the tumor microenvironment may influence BCG response, however this relationship … Read more

Cancer Immunol Res. 2026 Aug 4. doi: 10.1158/2326-6066.CIR-25-1285. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T cells have transformed cancer treatment, yet challenges for achieving broader clinical success remain, including overcoming tumor antigen heterogeneity and limited T-cell fitness. To address these challenges and enhance CAR T-cell functionality, we leveraged meditope technology, a lock-and-key … Read more

Cancer Immunol Res. 2026 Aug 4;14(8):1209. doi: 10.1158/2326-6066.CIR-14-8-WWR. NO ABSTRACT PMID:42548193 | DOI:10.1158/2326-6066.CIR-14-8-WWR

Cancer Immunol Res. 2026 Jul 31. doi: 10.1158/2326-6066.CIR-25-1639. Online ahead of print. ABSTRACT Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (ICI-IA). However, the mechanisms underlying ICI-IA, especially its recurrence, are not well understood. In this study, we sought to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal … Read more

Cancer Immunol Res. 2026 Jul 24. doi: 10.1158/2326-6066.CIR-25-1481. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) exhibits dense fibrosis and immune exclusion. While fibrosis has been studied globally and at the region-of-interest level, its impact on stromal-ductal architecture and immune cell localization remains unknown. Here, we establish cancer-associated fibroblast (CAF)-stratified ductal spatial architecture as … Read more

Cancer Immunol Res. 2026 Jul 22. doi: 10.1158/2326-6066.CIR-25-1230. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR)-T cell therapy has become a promising clinical approach against hematological malignancies, but patients receiving CAR-T cell therapy still presented inconsistent clinical outcomes and are complicated by incomplete tumor eradication. The gut microbiome has shown strong correlation with the … Read more

Cancer Immunol Res. 2026 Jul 22. doi: 10.1158/2326-6066.CIR-25-1493. Online ahead of print. ABSTRACT T cell exhaustion remains a barrier to adoptive cell therapies. Although γc cytokines are used to expand T cells, their impact on T cell states remains incompletely defined. Using an in vitro model of repetitive TCR stimulation, we found that high-dose IL-2 … Read more

Cancer Immunol Res. 2026 Jul 16. doi: 10.1158/2326-6066.CIR-25-1652. Online ahead of print. ABSTRACT It is well established that CD4⁺ T cells play a critical role in facilitating immune checkpoint therapy (ICT). Although CD4+ T-cell function in lymph nodes during CD8⁺ T-cell priming has been well investigated, their requirement at the effector phase in the tumor … Read more

Cancer Immunol Res. 2026 Jul 16. doi: 10.1158/2326-6066.CIR-25-1617. Online ahead of print. ABSTRACT In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy potentiates the effects of immune checkpoint inhibitors (ICIs) by activating the tumor-intrinsic innate immune response. However, ESCC cells frequently suppress this activation, which contributes to the high rates of immunotherapy resistance (70-80%) observed clinically. Thus, … Read more

Cancer Immunol Res. 2026 Jul 15. doi: 10.1158/2326-6066.CIR-25-0687. Online ahead of print. ABSTRACT Regulatory T cells (Treg) act as a powerful barrier to effective antitumor immunity. Although manipulating Treg is a promising anticancer strategy, doing so while sparing general immune tolerance has been a challenge. Identifying factors specifically expressed in tumor-infiltrating Treg is therefore important … Read more

Cancer Immunol Res. 2026 Jul 14. doi: 10.1158/2326-6066.CIR-25-0506. Online ahead of print. ABSTRACT Glioblastoma multiforme (GBM) is a lethal brain tumor with limited treatment options. Tumor-associated macrophages and microglia (TAMs) drive immune suppression and tumor progression, making them a key therapeutic target for GBM. Enhancing TAM phagocytosis in GBM has shown promise, particularly with innate … Read more

Cancer Immunol Res. 2026 Jul 9. doi: 10.1158/2326-6066.CIR-25-0777. Online ahead of print. ABSTRACT Intratumoral signaling via the cytosolic double-stranded RNA (dsRNA) receptors RIG-I and MDA-5 enhance antitumor immunity and can overcome resistance to cancer immunotherapy. Although BET proteins are established epigenetic drivers of immune escape mechanisms, their role in regulating RIG-I-like receptor (RLR) signaling remains … Read more

Cancer Immunol Res. 2026 Jul 8. doi: 10.1158/2326-6066.CIR-25-1475. Online ahead of print. ABSTRACT Focal radiotherapy can provide an in situ vaccine (ISV) effect that may prime adaptive antitumor immunity, which can be augmented by combination with intratumoral immune adjuvants and systemic immune checkpoint inhibition. However, propagation of an antitumor immune response is not consistently achieved … Read more

Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-26-0009. Online ahead of print. ABSTRACT Tumors remodel extracellular matrix (ECM) and glycosylation, yielding epitopes with restricted or limited detectability in normal adult tissues. Here, we evaluated the O-glycosylated IIICS domain of fibronectin (Tn-FN) as a chimeric antigen receptor (CAR) T cell target. FDC6-BBζ CAR T cells recognizing … Read more

Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-25-0794. Online ahead of print. ABSTRACT While mutant-specific KRAS inhibitors are approved to treat cancer, a deeper understanding of intratumoral changes driven specifically by KRAS inhibition is needed to maximize therapeutic responses. Here, we used single-cell RNA-seq, flow cytometry, and spatial transcriptomics to distinguish mechanisms of tumor control … Read more

Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-25-0175. Online ahead of print. ABSTRACT Tumor masses often exhibit heterogeneity, including escape variant clones that lack antigen-presenting machinery and/or tumor antigens, which poses a major challenge to immunotherapy. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been shown to effectively induce cell … Read more

Cancer Immunol Res. 2026 Jul 2. doi: 10.1158/2326-6066.CIR-25-1118. Online ahead of print. ABSTRACT Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with platinum resistance and poor outcomes in high-grade serous ovarian cancer (HGSOC), but the biological basis of this association remains unclear. We retrospectively analyzed 434 patients with HGSOC treated with platinum-based chemotherapy and found that … Read more

Cancer Immunol Res. 2026 Jul 2;14(7):1051. doi: 10.1158/2326-6066.CIR-14-7-WWR. NO ABSTRACT PMID:42388044 | DOI:10.1158/2326-6066.CIR-14-7-WWR

Cancer Immunol Res. 2026 Jun 30. doi: 10.1158/2326-6066.CIR-25-1602. Online ahead of print. ABSTRACT Macrophages constitute a dominant and functionally diverse immune population within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), yet how macrophage heterogeneity contributes to the tumor remains poorly defined. In an institutional cohort of 145 PDAC specimens, we identified a population of multinucleated … Read more

Cancer Immunol Res. 2026 Jun 29:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0635. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICI) have had a transformative impact on cancer treatment. However, many patients still fail to respond to ICIs, underscoring the need to identify novel drivers of resistance. In this issue, Ou and colleagues identify single-stranded DNA binding protein 4 … Read more

Cancer Immunol Res. 2026 Jun 26. doi: 10.1158/2326-6066.CIR-25-1611. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have transformed cancer care, at times generating durable partial or even complete responses in advanced cancers. However, only a minority of patients experience these “excellent” responses. Thus, there is a need for novel biomarkers that can identify those … Read more

Cancer Immunol Res. 2026 Jun 22. doi: 10.1158/2326-6066.CIR-25-1309. Online ahead of print. ABSTRACT The cancer intrinsic network controlling response to immune checkpoint blockade therapy remains elusive. Using a published single-cell RNA sequencing (scRNA-seq) dataset from breast cancer patients, we found that pre-therapy mRNA expression of NEDD8, which encodes the regulatory protein essential for neddylation, in … Read more

Cancer Immunol Res. 2026 Jun 17. doi: 10.1158/2326-6066.CIR-25-1626. Online ahead of print. ABSTRACT Pancreatic cancer responds poorly to immunotherapy, primarily due to poor activation of CD8+ T cells and their limited infiltration into the tumor tissue. Strategies to enhance CD8+ T-cell priming and function are therefore critical for improving immunotherapeutic efficacy in pancreatic cancer. The … Read more

Cancer Immunol Res. 2026 Jun 11. doi: 10.1158/2326-6066.CIR-25-1420. Online ahead of print. ABSTRACT Bispecific antibodies targeting tumor-associated antigens and CD3 are promising therapeutic agents for both solid and hematologic cancers. CD3-bispecifics induce T cell activation and cytotoxicity; however, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction, thereby limiting their full therapeutic … Read more

Cancer Immunol Res. 2026 Jun 11. doi: 10.1158/2326-6066.CIR-25-0998. Online ahead of print. ABSTRACT The Toll-like receptor (TLR) 7/8 agonist resiquimod shows promise for treating cutaneous T cell lymphoma and actinic keratosis, yet its mechanism of action remains unclear. We demonstrated that topical resiquimod significantly inhibited melanoma growth across various genetic and syngeneic mouse models, prolonged … Read more

Cancer Immunol Res. 2026 Jun 10. doi: 10.1158/2326-6066.CIR-25-1068. Online ahead of print. ABSTRACT Multiple myeloma (MM) is plasma cell malignancy that is mostly incurable, even with recent advances in treatment such as BCMA-targeted chimeric antigen receptor (CAR) T cells and bispecific T cell-engaging antibodies (TCEs). To better understand this treatment resistance, we examined MM cells … Read more

Cancer Immunol Res. 2026 Jun 8. doi: 10.1158/2326-6066.CIR-26-0335. Online ahead of print. ABSTRACT Endogenous circadian programs coordinate physiology across tissues, including immune cell trafficking and drug metabolism. Previous retrospective studies suggested that the timing of immune checkpoint inhibitor delivery may be a modifiable determinant of survival in patients with cancer, with earlier infusions often associated … Read more

Cancer Immunol Res. 2026 Jun 8. doi: 10.1158/2326-6066.CIR-25-1109. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have improved clear-cell renal cell carcinoma (ccRCC) therapy, yet many patients remain unresponsive. Alternative strategies are needed, and the HLA-G/ILT2 axis has emerged as a promising immunosuppressive pathway. Here, we deeply characterized CD8⁺ILT2⁺ tumor-infiltrating lymphocytes (TILs) as a … Read more

Cancer Immunol Res. 2026 Jun 2;14(6):899. doi: 10.1158/2326-6066.CIR-14-6-WWR. NO ABSTRACT PMID:42226639 | DOI:10.1158/2326-6066.CIR-14-6-WWR

Cancer Immunol Res. 2026 May 28. doi: 10.1158/2326-6066.CIR-25-1300. Online ahead of print. ABSTRACT A hallmark of pancreatic cancer is an extensive fibroinflammatory stroma. Myeloid cells, including abundant macrophages, are a prevalent cellular component of the pancreatic cancer microenvironment and a key driver of immunosuppression. Identifying mechanisms of myeloid-cell driven immunosuppression is thus key to developing … Read more

Cancer Immunol Res. 2026 May 21:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0513. Online ahead of print. ABSTRACT Sex differences in antitumor immunity contribute to disparities in cancer outcomes, yet the role of CD4+ T helper cells in this context remains poorly understood. In this issue, Hunt and colleagues show that sex hormones restrain CD4+ T-cell help in males, weakening … Read more

Cancer Immunol Res. 2026 May 15. doi: 10.1158/2326-6066.CIR-25-1490. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in hematologic malignancies but remains limited in solid tumors because of the immunosuppressive microenvironment, tumor heterogeneity, poor immune-cell infiltration, and progressive T-cell dysfunction. Because cytokine costimulation is critical for maintaining T-cell fitness, … Read more

Cancer Immunol Res. 2026 May 13. doi: 10.1158/2326-6066.CIR-25-1240. Online ahead of print. ABSTRACT In hepatocellular carcinoma (HCC), stromal and immune components shape invasion and metastasis. To identify the cellular states that drive extracellular matrix (ECM) remodeling, define their organization at the tumor margin, and evaluate their association with prognosis, we profiled stromal regions at the … Read more

Cancer Immunol Res. 2026 May 11. doi: 10.1158/2326-6066.CIR-25-0691. Online ahead of print. ABSTRACT CD19-directed chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, up to 60% of patients do not achieve a complete response. To uncover determinants of therapeutic efficacy, we analyzed the … Read more

Cancer Immunol Res. 2026 May 6. doi: 10.1158/2326-6066.CIR-25-0662. Online ahead of print. ABSTRACT Immune checkpoint blockade (ICB) therapy is transforming non-small cell lung cancer (NSCLC) treatment and prolonging overall survival (OS). However, not all patients are responsive. Using computational cytometry analysis to identify immune cell subsets and early dynamic changes, we aimed to unravel the … Read more

Cancer Immunol Res. 2026 May 5. doi: 10.1158/2326-6066.CIR-25-1321. Online ahead of print. ABSTRACT Osteosarcoma (OS) responds poorly to immune-checkpoint blockade (ICB), and the molecular drivers of its immune-cold state remain unclear. Using multi-omics analyses, we identified an immune-cold OS subtype characterized by enrichment of protein SUMOylation and found the SUMO E1 subunit UBA2 as a … Read more

Cancer Immunol Res. 2026 May 4;14(5):715. doi: 10.1158/2326-6066.CIR-14-5-WWR. NO ABSTRACT PMID:42076931 | DOI:10.1158/2326-6066.CIR-14-5-WWR

Cancer Immunol Res. 2026 Apr 29. doi: 10.1158/2326-6066.CIR-25-1312. Online ahead of print. ABSTRACT The immunosuppressive tumor microenvironment (TME) contributes to resistance against checkpoint inhibitors. However, the precise factors that shape the immune contexture of the TME remain elusive. Here, we report that Single-Stranded DNA Binding Protein 4 (SSBP4), a previously uncharacterized protein, suppresses intratumoral T-cell … Read more

Cancer Immunol Res. 2026 Apr 28. doi: 10.1158/2326-6066.CIR-25-0534. Online ahead of print. ABSTRACT Loss-of-function STK11 mutations occur in 15-20% of lung adenocarcinomas (LUAD) and correlate with immunotherapy failure and worse survival. By integrating analysis of human tumor samples, a human LUAD cell line panel, and CCLE and TCGA datasets, we found that C3 production was … Read more

Cancer Immunol Res. 2026 Apr 27. doi: 10.1158/2326-6066.CIR-25-0982. Online ahead of print. ABSTRACT The combination of multikinase inhibitors with PD-1 blockade therapy has emerged as a promising strategy to overcome resistance to PD-1 blockade monotherapy across multiple cancer types, including gastric cancer (GC). Here, we report that the multikinase inhibitor lenvatinib selectively reduced the number … Read more

Cancer Immunol Res. 2026 Apr 27. doi: 10.1158/2326-6066.CIR-25-0529. Online ahead of print. ABSTRACT Engineered T cell therapies, such as chimeric antigen receptor (CAR) and T cell receptor (TCR)-based approaches, have transformed outcomes in hematological malignancies, yet their efficacy in solid tumors remains limited by tumor antigen escape, immunosuppressive microenvironments, and insufficient activation of CAR or … Read more

Cancer Immunol Res. 2026 Apr 24. doi: 10.1158/2326-6066.CIR-25-1081. Online ahead of print. ABSTRACT Colorectal cancer (CRC) with liver metastases (CRCLM) remains a clinical challenge. CXCL13 is widely recognized as a biomarker of immunotherapy response. However, the functional heterogeneity (protumor vs. antitumor) of CXCL13⁺CD4⁺ T cell subsets has long been controversial. Through integrated analysis of single-cell … Read more

Cancer Immunol Res. 2026 Apr 23. doi: 10.1158/2326-6066.CIR-25-0388. Online ahead of print. ABSTRACT Accumulating evidence indicates that peritoneal macrophages, comprising resident peritoneal macrophages (resMØs) and monocyte-derived non-resident macrophages (moMØs), contribute to peritoneal tumor progression, by promoting tumor cell proliferation and migration, and driving immunosuppression. However, the mechanisms governing the expansion of resMØs and moMØs, as … Read more

Cancer Immunol Res. 2026 Apr 21:OF1-OF14. doi: 10.1158/2326-6066.CIR-25-1572. Online ahead of print. ABSTRACT Colorectal cancer remains a major global health burden and an area of urgent unmet medical need. Immunotherapy has shown limited success in colorectal cancer as most patients present with an immune-excluded, “cold” tumor microenvironment (TME). In this study, we report a dual-modality … Read more

Cancer Immunol Res. 2024 Nov 4;12(11):1491. doi: 10.1158/2326-6066.CIR-12-11-WWR. NO ABSTRACT PMID:42008778 | DOI:10.1158/2326-6066.CIR-12-11-WWR

Cancer Immunol Res. 2025 May 2;13(5):617. doi: 10.1158/2326-6066.CIR-13-5-WWR. NO ABSTRACT PMID:42008760 | DOI:10.1158/2326-6066.CIR-13-5-WWR

Cancer Immunol Res. 2026 Apr 13. doi: 10.1158/2326-6066.CIR-25-0816. Online ahead of print. ABSTRACT CD8+ T cell exhaustion limits the immune response to tumors because of ineffective T cell effector functions. Thus, therapies that inhibit T-cell exhaustion are critical for optimizing cancer treatment. Recent studies have implicated epigenetic proteins in T-cell exhaustion. Here, we identified activating … Read more

Cancer Immunol Res. 2026 Apr 10. doi: 10.1158/2326-6066.CIR-25-1073. Online ahead of print. ABSTRACT Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with low immunotherapy efficacy due to an immunosuppressive tumor microenvironment in proficient mismatch repair (pMMR) disease, which accounts for most cases of CRC. Herine, we have identified discoidin domain receptor 1 (DDR1) … Read more

Cancer Immunol Res. 2026 Apr 10. doi: 10.1158/2326-6066.CIR-25-0498. Online ahead of print. ABSTRACT Tumor-associated neutrophils (TANs) promote tumor growth and metastasis in hepatocellular carcinoma (HCC). Platelets can activate neutrophils and contribute to inflammation and organ damage; however, the relationship between TANs and platelets in HCC remains unclear. We performed multiplex immunohistochemistry and found that tumor-infiltrating … Read more

Cancer Immunol Res. 2026 Apr 2;14(4):527. doi: 10.1158/2326-6066.CIR-14-4-WWR. NO ABSTRACT PMID:41923516 | DOI:10.1158/2326-6066.CIR-14-4-WWR

Cancer Immunol Res. 2026 Mar 31:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0311. Online ahead of print. ABSTRACT The influence B cells have in the tumor microenvironment has historically remained unresolved across solid tumors. At the same time, numerous findings of ectopic germinal centers in inflamed tumors containing tertiary lymphoid structures have been the impetus for redefining what effective antitumor … Read more

Cancer Immunol Res. 2026 Mar 30. doi: 10.1158/2326-6066.CIR-25-1194. Online ahead of print. ABSTRACT Patients with bulky, unresectable stage III non-small cell lung cancer (NSCLC) face poor outcomes with standard concurrent chemoradiotherapy (cCRT) due to large radiation fields and toxicity risks. We evaluated the feasibility and efficacy of induction immunochemotherapy to downstage tumors prior to cCRT. … Read more

Cancer Immunol Res. 2026 Mar 25. doi: 10.1158/2326-6066.CIR-25-1115. Online ahead of print. ABSTRACT Sex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in coordinating antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cells provides … Read more

Cancer Immunol Res. 2026 Mar 20. doi: 10.1158/2326-6066.CIR-25-0609. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T cells have robust antitumor activity against hematologic malignancies and have the potential to benefit patients with solid tumors. Immune recognition of murine proteins expressed in adoptively transferred T cells and lack of homeostatic cytokines in the tumor … Read more

Cancer Immunol Res. 2026 Mar 19. doi: 10.1158/2326-6066.CIR-25-1138. Online ahead of print. ABSTRACT The variation in immunotherapy responses among patients with triple-negative breast cancer (TNBC) is attributed to the high heterogeneity of tumor immune components, in which macrophages play a key role. Hence, identification of key macrophage subpopulations associated with immunotherapy efficacy could provide important … Read more

Cancer Immunol Res. 2026 Mar 19. doi: 10.1158/2326-6066.CIR-25-0605. Online ahead of print. ABSTRACT FOXM1 is highly expressed in various cancer types and considered a key driver of cancer progression. Accordingly, we evaluated the immunogenicity of FOXM1 and investigated the feasibility of targeting this transcription factor using T cell receptor (TCR) engineering. We identified epitopes derived … Read more

Cancer Immunol Res. 2026 Mar 17. doi: 10.1158/2326-6066.CIR-24-1216. Online ahead of print. ABSTRACT In humans and mice, the T cell receptor (TCR) of each effector/memory T cell clone recognizes from one to several cognate peptide-MHC complexes (pMHC). Limited knowledge on TCR repertoire specificities restricts our capacity to rationally interpret this information, both diagnostically and in … Read more

Cancer Immunol Res. 2026 Mar 13. doi: 10.1158/2326-6066.CIR-25-0651. Online ahead of print. ABSTRACT Interleukin-1 (IL-1) plays dual functions in cancer. It promotes cancer-related inflammation and progression, but also influences leukocyte functional activation. IL-1 receptor 2 (IL-1R2) functions as an IL-1 decoy receptor, inhibiting IL-1 activity. Here, we investigated the contribution of IL-1R2 in tuning IL-1-dependent … Read more

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