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    Home > Active Ingredient News > Antitumor Therapy > Nat Commun: Notch signaling pathway affects the efficacy of immune checkpoint blockade in patients with recurrent small cell lung cancer

    Nat Commun: Notch signaling pathway affects the efficacy of immune checkpoint blockade in patients with recurrent small cell lung cancer

    • Last Update: 2021-07-31
    • Source: Internet
    • Author: User
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    Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine (NE) cancer that accounts for approximately 15% of all lung cancer types.
    In the United States alone, the annual incidence of the disease exceeds 34,000
    .


    The standard of treatment for SCLC includes platinum and etoposide (etoposide) chemotherapy strategies.


    Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine (NE) cancer, which accounts for about 15% of all lung cancer types.


    SCLC is characterized by functional p53 and RB12 loss mutants and high tumor burden (TMB), which also indicates that the tumor may have immune immunogenic and an immune checkpoint block (the ICB) responsive to therapy
    .

    immunity

    However, previous studies have shown that immune checkpoint blockade (ICB) only benefits a small number of SCLC patients, and its underlying mechanism is not clear
    .

    Immune checkpoint blockade (ICB) benefits only a small proportion of SCLC patients, and its underlying mechanism is not clear
    .


    Immune checkpoint blockade (ICB) benefits only a small proportion of SCLC patients, and its underlying mechanism is not clear


    Result analysis of recurrent small cell lung cancer discovery cohort

    Result analysis of recurrent small cell lung cancer discovery cohort

    To determine the relevant predictors of ICB clinical benefit, the researchers performed immunogenomics analysis on tumor samples from patients with recurrent SCLC
    .


    The results showed that the tumor tissues of patients who benefited from ICB therapy showed cytotoxic T cell infiltration, high expression levels of APM (antigen processing and presentation mechanism) genes, and low neuroendocrine (NE) differentiation


    The tumor tissues of patients who benefited from ICB therapy showed cytotoxic T cell infiltration, high expression levels of APM (antigen processing and presentation mechanism) genes, and low neuroendocrine (NE) differentiation


    The level of Notch signaling pathway is related to the clinical benefit of immune checkpoint blockade

    The level of Notch signaling pathway is related to the clinical benefit of immune checkpoint blockade

    Further studies have shown that the increase of Notch signal is positively correlated with lower NE differentiation status, and this factor can most significantly predict the clinical benefit of ICB treatment
    .


    Activation of Notch signaling in human NE SCLC cell lines induces a low NE differentiation phenotype, which is marked by increased APM gene expression, which also indicates the activation of Notch signaling, low NE differentiation status, and increased tumor intrinsic There is a certain correlation between immunity


    The increase of Notch signal is positively correlated with lower NE differentiation status, and this factor can most significantly predict the clinical benefit of ICB treatment




    Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer.


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