Cancer Immunology Reserch

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

Peripheral Th17 immune signature associates with excellent response to anti-PD1/anti-PD-L1 therapy across solid tumors

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Cancer Immunol Res. 2026 Jun 26. doi: 10.1158/2326-6066.CIR-25-1611. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have transformed cancer care, at times generating durable partial or even complete responses in advanced cancers. However, only a minority of patients experience these “excellent” responses. Thus, there is a need for novel biomarkers that can identify those … Read more

Cancer intrinsic protein neddylation modulates the intra-tumoral immune landscape to constrain immune checkpoint blockade therapy

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Cancer Immunol Res. 2026 Jun 22. doi: 10.1158/2326-6066.CIR-25-1309. Online ahead of print. ABSTRACT The cancer intrinsic network controlling response to immune checkpoint blockade therapy remains elusive. Using a published single-cell RNA sequencing (scRNA-seq) dataset from breast cancer patients, we found that pre-therapy mRNA expression of NEDD8, which encodes the regulatory protein essential for neddylation, in … Read more

ADAR1 deficiency in pancreatic cancer cells potentiates cDC1 activation and promotes sensitization to immunotherapy

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Cancer Immunol Res. 2026 Jun 17. doi: 10.1158/2326-6066.CIR-25-1626. Online ahead of print. ABSTRACT Pancreatic cancer responds poorly to immunotherapy, primarily due to poor activation of CD8+ T cells and their limited infiltration into the tumor tissue. Strategies to enhance CD8+ T-cell priming and function are therefore critical for improving immunotherapeutic efficacy in pancreatic cancer. The … Read more

DNA hypomethylating agents preserve T cell stemness and potentiate the efficacy of CD3-bispecific antibodies

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Cancer Immunol Res. 2026 Jun 11. doi: 10.1158/2326-6066.CIR-25-1420. Online ahead of print. ABSTRACT Bispecific antibodies targeting tumor-associated antigens and CD3 are promising therapeutic agents for both solid and hematologic cancers. CD3-bispecifics induce T cell activation and cytotoxicity; however, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction, thereby limiting their full therapeutic … Read more

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