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#肿瘤微环境

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Oct 10Sat
  1. medicalxpress.com65

    Tracking molecular malfunctions in metastatic colorectal cancer to find new avenues for treatment

    Hokkaido University researchers, working with an international team led by University of South Florida Health and Tampa General Hospital, have shown that the 30-year-old sphingolipid rheostat model operates in the tumor microenvironment rather than inside cancer cells in metastatic colorectal cancer. Analysis of 574 human colon cancer tissue samples showed that rising sphingosine-1-phosphate and falling long-chain ceramide create a biochemical barrier that excludes cytotoxic T cells. In lab experiments, blocking S1P/S1PR3 let killer T cells attack tumors again, pointing to a combination strategy with immunotherapy.

    Why it matters: It explains a mechanism of immunotherapy resistance in metastatic colorectal cancer and identifies a druggable pathway.

Oct 1Thu
  1. Oncoimmunology58

    A novel oncolytic peptide synergizing with immunotherapy

    Yuan et al. described in Nature an acid-responsive membranolytic peptide that separates lysosomal rupture from later plasma membrane rupture, turning oncolysis into immunogenic cell death. The design allows systemic administration, induces antigen-specific immunity and sensitizes tumors to programmed death ligand 1 blockade with limited toxicity.

    Why it matters: A preclinical Nature study shows an oncolytic peptide design that sensitizes tumors to PD-L1 blockade.

Aug 18Tue
  1. Cancer Cell62

    Your neighbors matter: Adjacent cancer cells dampen TLS function.

    Hernández-Verdin et al. show that cancer-derived gamma-aminobutyric acid (GABA) acts as an immunosuppressant factor that renders tertiary lymphoid structures (TLSs) dysfunctional and drives resistance to immunotherapy in some tumors. Targeting GABA together with immunotherapy reshaped the tumor and TLS microenvironment and improved therapeutic efficacy. The work points to GABA as a candidate target for overcoming TLS-associated immunotherapy resistance.

    Why it matters: Identifies a mechanism of immunotherapy resistance and a targetable candidate, GABA, in TLS biology.

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