Tumor cell-intrinsic Decr2 regulates ferroptosis and immunotherapy efficacy

Cancer Immunol Res. 2025 Jun 13. doi: 10.1158/2326-6066.CIR-24-0519. Online ahead of print. ABSTRACT Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants resistant … Read more

Inhibition of eEF-2K enhances the antitumor efficacy of NK cells

Cancer Immunol Res. 2025 Jun 12. doi: 10.1158/2326-6066.CIR-24-1001. Online ahead of print. ABSTRACT NK cells are increasingly being evaluated for their utility in cancer immunotherapy. However, their efficacy is often attenuated in the cancer microenvironment. The identification of additional checkpoint molecules that limit NK-cell function is crucial to further development of NK cell-based therapies. Herein, … Read more

Discovery of BMS-986408, a First-In-Class Dual DGKα and DGKζ Inhibitor That Unleashes PD-1 Checkpoint and CAR T-Cell Immunotherapies

Cancer Immunol Res. 2025 Jun 12. doi: 10.1158/2326-6066.CIR-25-0156. Online ahead of print. ABSTRACT Diacylglycerol kinase α (DGKα) and DGKζ are lipid kinases that negatively regulate T-cell signaling through diacylglycerol (DAG) metabolism, making them attractive targets for next-generation immunotherapy. Here, we report the discovery and pre-clinical characterization of the clinical-stage DGKα and DGKζ lipid kinase inhibitor, … Read more

Artificial Intelligence Can Predict Personalized Immunotherapy Outcomes in Cancer

Cancer Immunol Res. 2025 Jun 10:OF1-OF14. doi: 10.1158/2326-6066.CIR-24-1270. Online ahead of print. ABSTRACT The rapid advancement of artificial intelligence (AI) technologies has opened new avenues for advancing personalized immunotherapy in cancer treatment. This review highlights current research progress in applying AI to optimize the use of immunotherapy for patients with cancer. Recent studies demonstrate that … Read more

Sustained macrophage reprogramming is required for CD8+ T cell-dependent long-term tumor eradication

Cancer Immunol Res. 2025 Jun 5. doi: 10.1158/2326-6066.CIR-24-0797. Online ahead of print. ABSTRACT Tumor-associated macrophages (TAMs) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 … Read more

CTG-initiated cryptic peptide translation up and downstream of a canonical ATG start codon is enhanced by TLR stimulation and induces tumor regression in mice

Cancer Immunol Res. 2025 Jun 3. doi: 10.1158/2326-6066.CIR-24-0467. Online ahead of print. ABSTRACT Cytotoxic T-lymphocytes (CTLs) screen cells for signs of infection and transformation by recognizing peptides displayed on major histocompatibility complex (MHC) class I molecules. Next to canonical ATG-initiated open reading frames (ORFs), non-canonical translation can result in synthesis of non-conventional or `cryptic´ polypeptides. … Read more

Secretion of a VEGF-blocking scFv enhances CAR T-cell potency

Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-0876. Online ahead of print. ABSTRACT CAR T-cell therapy is an effective treatment strategy in B-cell malignancies, however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature, however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic … Read more

Single-cell analysis of post-translational modifications identifies immunosuppressive macrophage subtypes in the HBV-positive hepatocellular carcinoma microenvironment

Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-1298. Online ahead of print. ABSTRACT Analysis of post-translational modifications (PTMs) of proteins can provide new insight, beyond that obtained from analysis of protein levels, for understanding the tumor microenvironment (TME). The characteristics of PTMs in immune cells, along with their spatial distribution, have not been comprehensively integrated, … Read more

The effects of clinically relevant radionuclides on the activation of a type I interferon response correlate with radionuclide half-life and linear energy transfer and influence radiopharmaceutical antitumor efficacy

Cancer Immunol Res. 2025 May 29. doi: 10.1158/2326-6066.CIR-24-1191. Online ahead of print. ABSTRACT Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90Y, 177Lu, and 225Ac in vitro as unbound radionuclides and … Read more

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