Cancer Immunology Reserch

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

Topical resiquimod elicits systemic protection and improves anti-PD1 therapy in melanoma via priming of CD8+ T cells

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Cancer Immunol Res. 2026 Jun 11. doi: 10.1158/2326-6066.CIR-25-0998. Online ahead of print. ABSTRACT The Toll-like receptor (TLR) 7/8 agonist resiquimod shows promise for treating cutaneous T cell lymphoma and actinic keratosis, yet its mechanism of action remains unclear. We demonstrated that topical resiquimod significantly inhibited melanoma growth across various genetic and syngeneic mouse models, prolonged … Read more

Multiple Myeloma Cells Resistant to T-cell Therapies Exhibits a CD45+ Immune Evasive Phenotype

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Cancer Immunol Res. 2026 Jun 10. doi: 10.1158/2326-6066.CIR-25-1068. Online ahead of print. ABSTRACT Multiple myeloma (MM) is plasma cell malignancy that is mostly incurable, even with recent advances in treatment such as BCMA-targeted chimeric antigen receptor (CAR) T cells and bispecific T cell-engaging antibodies (TCEs). To better understand this treatment resistance, we examined MM cells … Read more

Cancer chemo-immunotherapy: time will tell

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Cancer Immunol Res. 2026 Jun 8. doi: 10.1158/2326-6066.CIR-26-0335. Online ahead of print. ABSTRACT Endogenous circadian programs coordinate physiology across tissues, including immune cell trafficking and drug metabolism. Previous retrospective studies suggested that the timing of immune checkpoint inhibitor delivery may be a modifiable determinant of survival in patients with cancer, with earlier infusions often associated … Read more

ILT2 identifies an unexploited pool of intratumoral CD8+ bystander T cells with TCR-independent cytotoxicity in renal cell carcinoma

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Cancer Immunol Res. 2026 Jun 8. doi: 10.1158/2326-6066.CIR-25-1109. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICIs) have improved clear-cell renal cell carcinoma (ccRCC) therapy, yet many patients remain unresponsive. Alternative strategies are needed, and the HLA-G/ILT2 axis has emerged as a promising immunosuppressive pathway. Here, we deeply characterized CD8⁺ILT2⁺ tumor-infiltrating lymphocytes (TILs) as a … Read more

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