TGF-{beta}1 drives neutrophil extracellular traps formation to promote CD8+ T cell exhaustion via the ERK-c-Fos-JunB axis, mediating gastric cancer immunotherapy resistance

Background
Resistance to anti-programmed cell death protein-1 (PD-1) treatment in gastric cancer (GC) is closely associated with an immunosuppressive tumor microenvironment. However, the role of neutrophils in resistance to anti-PD-1 therapy remains u…

{beta}-glucan elicits APOE-dependent peripheral trained immunity to suppress hepatocellular carcinoma

Background
Although immunotherapy has revolutionized cancer treatment, hepatocellular carcinoma (HCC) continues to demonstrate limited clinical responses, highlighting the urgent need for novel immunomodulatory strategies. Trained immunity, an emergin…

Efficient discovery of an agonistic anti-OX40 nanobody by epitope-directed approach to address enrichment-driven epitope bias

Background
Conventional antibody discovery approaches that do not account for enrichment-driven biases, such as epitope immunogenicity, PCR amplification bias, or protein expression efficiency, may result in under-representation of rare yet functional…

Myosin VI drives breast cancer progression via SP1/CA9-mediated acidic tumor microenvironment remodeling and subsequent M2 macrophage polarization

Background
The acidic tumor microenvironment (TME) is a major driver of immunosuppression and tumor progression in breast cancer. Although myosin VI (MYO6), an actin-dependent motor protein, is frequently upregulated in malignancies, its function in i…

Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer

Background
Cancer-associated mesothelial cells (CAMCs) are key modulators of the ovarian tumor microenvironment, contributing to tumor growth and immune evasion. Mesothelial cells (MCs) maintain peritoneal homeostasis and immune surveillance and repre…

Adipocyte-derived LTB4 programs human NKG2A+ {gamma}{delta} T cells as cytotoxic sentinels at the adipose-tumor interface in breast cancer

Background
The peritumoral microenvironment has emerged as a key role in affecting tumor invasion and immunotherapy responses. In adipose-enriched tumors, such as breast cancer (BC), peritumoral adipose tissue (PA) harbors unconventional immune popula…

Targeting TOMM40 unleashes immunogenic mitophagy to facilitate antigen presentation and immunotherapy sensitization

Background
Mitophagy is a mitochondrial quality control process that maintains cellular homeostasis in cancer, yet whether its dysregulation can be exploited to induce tumor immunogenicity remains unclear.

Methods
We integrated pancancer single-cell …

Intrinsic tumor cell line immunogenicity may drive CAR-independent T cell responses and confound CAR T cell preclinical modeling

Background
Chimeric antigen receptor (CAR) T cells are highly potent therapies approved by the U.S. Food and Drug Administration (FDA) for several hematological malignancies. However, efficacy remains variable due to resistance, antigen modulation, sy…

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