DNA hypomethylating agents preserve T cell stemness and potentiate the efficacy of CD3-bispecific antibodies

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

Topical resiquimod elicits systemic protection and improves anti-PD1 therapy in melanoma via priming of CD8+ T cells

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

Multiple Myeloma Cells Resistant to T-cell Therapies Exhibits a CD45+ Immune Evasive Phenotype

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 chemo-immunotherapy: time will tell

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

ILT2 identifies an unexploited pool of intratumoral CD8+ bystander T cells with TCR-independent cytotoxicity in renal cell carcinoma

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

Targeting CCR1 remodels the tumor microenvironment and relieves immune suppression in pancreatic cancer

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

Help! Male Hormones Dampen CD4+ T-cell Help in Cancer

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

Reprogramming CAR with cytokine signaling increases the efficacy of CAR-T cell therapy in solid tumour treatment and confers sustained immune memory

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

Hypoxia-induced ADAM8⁺ macrophages and FAP⁺ fibroblasts form an extracellular matrix-remodeling niche at the tumor boundary in HCC

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

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