Constitutive STAT3 signaling, in comparison to STAT5, enhances CAR T cell efficacy and lowers systemic toxicity

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

Integrated Single-Cell Profiling Reveals Dichotomous NK Cell Populations Associated with Immunosuppression in Solid Tumors

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

Loss of miR-29a/b1 cluster reprograms the tumor microenvironment and contributes to immunosuppression in lung cancer

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

Intra-tumoral tertiary lymphoid structures characterized by a B cell-related signature elicit antitumor effect through HAPLN3 in hepatocellular carcinoma

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

VSIG4 restricts hepatocellular carcinoma control by suppressing tumor-specific CD8+ T cell immunity in the tumor microenvironment

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

Engineered CCR7 overexpression enhances nodal CAR-T cell homing and cytotoxicity toward B cell lymphoma

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

Baseline tumor features and systemic immune dynamics underlying efficacy in MSS metastatic colorectal cancer treated with regorafenib, ipilimumab, and nivolumab

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

Potent cytotoxic tumor-infiltrating lymphocytes can be generated from immune-excluded chondrosarcomas using regulatable membrane-bound IL15

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

CLK1 Promotes Myeloid-Derived Suppressor Cell Trafficking and Reprograms the Tumor Microenvironment by activating Hippo/YAP signaling in Colorectal Cancer

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

Ex vivo expansion of melanoma tumor infiltrating lymphocytes leads to a dominant exhausted T cell population with lack of memory markers

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

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