Bicistronic CAR-T Cell against BCMA and CD229 effectively controls myeloma even when BCMA expression is limited

Cancer Immunol Res. 2025 Jun 27. doi: 10.1158/2326-6066.CIR-24-1313. Online ahead of print. ABSTRACT Anti-BCMA CAR-T cell therapy has revolutionized the prognosis of relapsed / refractory multiple myeloma patients. Regrettably, despite unprecedented overall response rates achieved with this approach, most patients eventually relapse. One of the primary reasons for this is the complete loss or reduced … Read more

SF3B1K700E neoantigen is a CD8+ T-cell target shared across human myeloid neoplasms

Cancer Immunol Res. 2025 Jun 26. doi: 10.1158/2326-6066.CIR-24-0091. Online ahead of print. ABSTRACT Acquired mutations in spliceosome genes in early hematopoietic stem/progenitor cells are common events in myelodysplastic neoplasms (MDS) and related myeloid malignancies. Mutations in the spliceosome factor subunit B1 (SF3B1) gene occur in ≥20% of MDS cases at conserved hotspots and in early … Read more

GPC2-targeted CAR T cells engineered with NFAT-inducible membrane-tethered IL-15/IL-21 exhibit enhanced activity against neuroblastoma

Cancer Immunol Res. 2025 Jun 26. doi: 10.1158/2326-6066.CIR-24-0975. Online ahead of print. ABSTRACT Neuroblastoma (NB) is a highly aggressive childhood solid tumor with poor outcomes. Chimeric antigen receptor (CAR) T cells have shown limited efficacy in NB, with the best outcomes reported in patients with a low tumor burden, highlighting the need for further CAR … Read more

RORγt Inhibition Reduces Pro-Tumor Inflammation and Decreases Tumor Growth in Experimental Models of Lung Cancer

Cancer Immunol Res. 2025 Jun 18. doi: 10.1158/2326-6066.CIR-24-1128. Online ahead of print. ABSTRACT The retinoic acid receptor-related orphan receptor C (RORC) gene encodes two isoforms, RORγ and RORγt, which function as transcription factors in different cell types. RORγt is expressed in specific immune cells involved in inflammatory responses, while RORγ is found in parenchymal cells, … Read more

In vivo labelling resolves distinct temporal, spatial, and functional properties of tumour macrophages, and identifies subset-specific effects of PD-L1 blockade

Cancer Immunol Res. 2025 Jun 16. doi: 10.1158/2326-6066.CIR-24-1233. Online ahead of print. ABSTRACT Tumour-associated macrophages (TAMs) are a universal feature of cancers but variably influence outcome and treatment responses. Here, we used a photoconvertible mouse to distinguish newly entering, monocyte-derived (md)TAMs that were enriched at the tumour core, from resident-like (r)TAMs that localised with fibroblasts … Read more

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

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