Cancer Immunology Reserch

A Patient-Derived Screen Identifies HDAC Inhibitors as Enhancers of Phagocytosis and Potent Immunotherapy Partners

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Cancer Immunol Res. 2026 Jul 14. doi: 10.1158/2326-6066.CIR-25-0506. Online ahead of print. ABSTRACT Glioblastoma multiforme (GBM) is a lethal brain tumor with limited treatment options. Tumor-associated macrophages and microglia (TAMs) drive immune suppression and tumor progression, making them a key therapeutic target for GBM. Enhancing TAM phagocytosis in GBM has shown promise, particularly with innate … Read more

BET inhibition synergizes with RLR signaling to enhance tumor immunogenicity and T cell recognition

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Cancer Immunol Res. 2026 Jul 9. doi: 10.1158/2326-6066.CIR-25-0777. Online ahead of print. ABSTRACT Intratumoral signaling via the cytosolic double-stranded RNA (dsRNA) receptors RIG-I and MDA-5 enhance antitumor immunity and can overcome resistance to cancer immunotherapy. Although BET proteins are established epigenetic drivers of immune escape mechanisms, their role in regulating RIG-I-like receptor (RLR) signaling remains … Read more

In situ vaccination, low-dose targeted radionuclide therapy, and immune checkpoint inhibition eradicate poorly immunogenic metastatic tumors in murine cancer models

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Cancer Immunol Res. 2026 Jul 8. doi: 10.1158/2326-6066.CIR-25-1475. Online ahead of print. ABSTRACT Focal radiotherapy can provide an in situ vaccine (ISV) effect that may prime adaptive antitumor immunity, which can be augmented by combination with intratumoral immune adjuvants and systemic immune checkpoint inhibition. However, propagation of an antitumor immune response is not consistently achieved … Read more

CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance

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Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-26-0009. Online ahead of print. ABSTRACT Tumors remodel extracellular matrix (ECM) and glycosylation, yielding epitopes with restricted or limited detectability in normal adult tissues. Here, we evaluated the O-glycosylated IIICS domain of fibronectin (Tn-FN) as a chimeric antigen receptor (CAR) T cell target. FDC6-BBζ CAR T cells recognizing … Read more

Coordinated immune activation following KRAS inhibition in syngeneic models reveals molecular pathways that potentiate and limit antitumor immunity

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Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-25-0794. Online ahead of print. ABSTRACT While mutant-specific KRAS inhibitors are approved to treat cancer, a deeper understanding of intratumoral changes driven specifically by KRAS inhibition is needed to maximize therapeutic responses. Here, we used single-cell RNA-seq, flow cytometry, and spatial transcriptomics to distinguish mechanisms of tumor control … Read more

Enhancement of ferroptosis in escape variant tumor cells by IFN-γ derived from antigen-specific T cells controls tumor with heterogeneity

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Cancer Immunol Res. 2026 Jul 3. doi: 10.1158/2326-6066.CIR-25-0175. Online ahead of print. ABSTRACT Tumor masses often exhibit heterogeneity, including escape variant clones that lack antigen-presenting machinery and/or tumor antigens, which poses a major challenge to immunotherapy. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been shown to effectively induce cell … Read more

VISTA+ neutrophils contribute to platinum resistance by suppressing CD8+T cells in high-grade serous ovarian cancer

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Cancer Immunol Res. 2026 Jul 2. doi: 10.1158/2326-6066.CIR-25-1118. Online ahead of print. ABSTRACT Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with platinum resistance and poor outcomes in high-grade serous ovarian cancer (HGSOC), but the biological basis of this association remains unclear. We retrospectively analyzed 434 patients with HGSOC treated with platinum-based chemotherapy and found that … Read more

Multinucleated giant cells in human pancreatic cancer are a distinct macrophage population undergoing a DNA damage response and associated with an aggressive tumor microenvironment

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Cancer Immunol Res. 2026 Jun 30. doi: 10.1158/2326-6066.CIR-25-1602. Online ahead of print. ABSTRACT Macrophages constitute a dominant and functionally diverse immune population within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), yet how macrophage heterogeneity contributes to the tumor remains poorly defined. In an institutional cohort of 145 PDAC specimens, we identified a population of multinucleated … Read more

Fueling Immunotherapy Resistance: SSBP4 Links Tumor Cholesterol Biosynthesis to Immune Evasion

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Cancer Immunol Res. 2026 Jun 29:OF1-OF2. doi: 10.1158/2326-6066.CIR-26-0635. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICI) have had a transformative impact on cancer treatment. However, many patients still fail to respond to ICIs, underscoring the need to identify novel drivers of resistance. In this issue, Ou and colleagues identify single-stranded DNA binding protein 4 … Read more

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