Cancer Immunology Reserch

Periductal Fibroblast Density Defines Lymphocyte Exclusion via a CD44-Dependent Stromal Checkpoint in Pancreatic Cancer

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Cancer Immunol Res. 2026 Jul 24. doi: 10.1158/2326-6066.CIR-25-1481. Online ahead of print. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) exhibits dense fibrosis and immune exclusion. While fibrosis has been studied globally and at the region-of-interest level, its impact on stromal-ductal architecture and immune cell localization remains unknown. Here, we establish cancer-associated fibroblast (CAF)-stratified ductal spatial architecture as … Read more

The Gut Microbiome Drives Endogenous T Cell Activation Following CAR-T Cell Therapy

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Cancer Immunol Res. 2026 Jul 22. doi: 10.1158/2326-6066.CIR-25-1230. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR)-T cell therapy has become a promising clinical approach against hematological malignancies, but patients receiving CAR-T cell therapy still presented inconsistent clinical outcomes and are complicated by incomplete tumor eradication. The gut microbiome has shown strong correlation with the … Read more

In vitro inhibition of STAT5 signaling limits CD8⁺ T cell exhaustion and improves outcomes in adoptive T-cell therapy

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Cancer Immunol Res. 2026 Jul 22. doi: 10.1158/2326-6066.CIR-25-1493. Online ahead of print. ABSTRACT T cell exhaustion remains a barrier to adoptive cell therapies. Although γc cytokines are used to expand T cells, their impact on T cell states remains incompletely defined. Using an in vitro model of repetitive TCR stimulation, we found that high-dose IL-2 … Read more

CD4+ T cells play distinct roles during the priming versus effector phases of immune checkpoint therapy-dependent tumor elimination by CD8+ T cells

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Cancer Immunol Res. 2026 Jul 16. doi: 10.1158/2326-6066.CIR-25-1652. Online ahead of print. ABSTRACT It is well established that CD4⁺ T cells play a critical role in facilitating immune checkpoint therapy (ICT). Although CD4+ T-cell function in lymph nodes during CD8⁺ T-cell priming has been well investigated, their requirement at the effector phase in the tumor … Read more

Elevated CHAF1A suppresses type I interferon production and causes immunotherapy resistance in esophageal squamous cell carcinoma

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Cancer Immunol Res. 2026 Jul 16. doi: 10.1158/2326-6066.CIR-25-1617. Online ahead of print. ABSTRACT In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy potentiates the effects of immune checkpoint inhibitors (ICIs) by activating the tumor-intrinsic innate immune response. However, ESCC cells frequently suppress this activation, which contributes to the high rates of immunotherapy resistance (70-80%) observed clinically. Thus, … Read more

Tim-3 Sustains Tumor Treg Stability and Function, Limiting Checkpoint Blockade Therapy Efficacy

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Cancer Immunol Res. 2026 Jul 15. doi: 10.1158/2326-6066.CIR-25-0687. Online ahead of print. ABSTRACT Regulatory T cells (Treg) act as a powerful barrier to effective antitumor immunity. Although manipulating Treg is a promising anticancer strategy, doing so while sparing general immune tolerance has been a challenge. Identifying factors specifically expressed in tumor-infiltrating Treg is therefore important … Read more

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

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