USP1-mediated lipophagy-lipogenesis axis drives cholangiocarcinoma progression and immune evasion

Background
Cholangiocarcinoma (CCA), a malignancy arising from biliary epithelial cells, features a tumor microenvironment (TME) characterized by metabolic dysregulation and immunosuppression. Although diverse metabolic aberrations have been observed,…

VSIG4 suppresses antitumor T cell immunity via the SLC3A2-dependent metabolic-ionic checkpoint

Background
Immune checkpoint blockade therapy aims to restore T-cell function within the tumor microenvironment (TME), eliciting durable antitumor responses. However, clinical response rates to PD-1/PD-L1 inhibitors remain limited, particularly in imm…

From viral drift to tumor drift: why cancer immunotherapy needs B cells and dynamic adaptation

Current T-cell-based immunotherapies—chimeric antigen receptor T (CAR-T) cells, checkpoint inhibitors, and neoantigen vaccines—share a fundamental vulnerability: they target fixed antigens while tumors continuously evolve. Like influenza v…

CD19/CD22 bivalent CAR T cells in children, adolescents and young adults with B-ALL: final phase 1 trial results

Multiantigen targeting chimeric antigen receptor (CAR) T cells have emerged as a strategy to mitigate antigen escape observed after single antigen targeting therapy. Our initial experience with a bivalent CD19.22.BB CAR T-cell construct in children, a…

Targeting B7-H3 in patients with metastatic triple-negative breast cancer and brain metastases: an opportunity to “revive” immunotherapy as a treatment strategy?

Approximately one-third of patients with metastatic triple-negative breast cancer (TNBC) develop brain metastases during their lifetime. Notably, up to 90% of TNBC brain metastases express B7-H3, a molecule that contributes to an immunosuppressive mic…

Inhibition of histone demethylase LSD1 suppresses CD47 expression and enhances efficacy of CD47 blockade in breast cancer

Background
CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by …

Glucose restriction reprograms lipid metabolism and enhances immunotherapy through ZNRF3-Wnt-SCD signaling axis

Background
Glucose restriction is a hallmark of the tumor microenvironment (TME), yet how tumor cells adapt to this metabolic stress and the impact of metabolic reprogramming on the TME remains incompletely understood.

Methods
A genome-wide CRISPR kn…

Repurposing COVID-19 (and other) mRNA vaccines to boost cancer immunotherapy efficacy: mechanistic insights and future directions

A recent study by Grippin et al showed that COVID-19 mRNA-lipid nanoparticle vaccines can be strategically implemented to fundamentally reshape the immunosuppressive tumor microenvironment and boost the efficacy of immune checkpoint inhibitors (ICIs) …

Novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity

Background
While chimeric antigen receptor (CAR) T cells have achieved encouraging remission rates in hematological malignancies, they have demonstrated limited success in treating glioblastoma (GBM), particularly due to high intratumoral and intertum…

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