Altered thymopoiesis in thymoma is associated with defects in negative selection machinery and decreased Treg abundance

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

Circulating neoantigen- and viral oncoprotein-specific CD8+ T cells share a transcriptional signature

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

Targeting SALL4 with an HLA Class I-restricted TCR for cancer immunotherapy

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

HNRNPA2B1 orchestrates immune evasion in colorectal cancer by rewiring tumor-immune cell interactions and suppressing CD8+ T cell infiltration

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

Single-cell clonal lineage tracing identifies the transcriptional program controlling the cell-fate decisions by neoantigen-specific CD8+ T cells

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

IL-2/IL-15 signaling induces NK cell production of FLT3LG augmenting anti-PD-1 immunotherapy

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

CAR-ving a Path: Metalloprotease-Engineered CAR T Cells Tunnel through Solid Tumors

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

Antibody Mediated Inhibition of HLA/LILR Interactions Breaks Innate Immune Tolerance and Induces Antitumor Immunity

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

CD4+ T cells mediate MHC-deficient tumor rejection and endothelial cell reprogramming

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

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