We are analyzing https://link.springer.com/article/10.1007/s12105-017-0857-3.

Title:
Beyond the Percentages of PD-L1-Positive Tumor Cells: Induced Versus Constitutive PD-L1 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma | Head and Neck Pathology
Description:
Anti-PD1 antibody has been approved for metastatic squamous cell carcinoma of the head and neck (SCCHN) and objective response rates of approximately 20% have been reported. Defining PD-L1 expression at ≥ 1% tumor cells as positive, PD-L1-positive tumors showed a higher response rate. However, it is unclear whether 1% is the optimal cutoff, and studies on lung cancer suggested 50% cutoff as a stronger predictive biomarker. 96 primary SCCHN from oropharynx and oral cavity and 34 corresponding metastatic lesions were typed for membranous PD-L1 expression. p16 immunohistochemistry was used as a surrogate marker for HPV status in SCCHN from the oropharynx. Fifty-two of 96 (54%) tumors were PD-L1-positive, 72% if PD-L1 expression in tumor-infiltrating immunocytes was also included as positive. Fifteen of 34 primary-metastasis tumor pairs differed in PD-L1 expression, and p16(+) cases more frequently showed PD-L1 expression in immunocytes than p16(−) cases (82 vs. 45%, p < 0.05). PD-L1-positive SCCHN showed two distinct patterns of expression. In the induced pattern of expression, PD-L1-positive tumor cells were limited to the periphery of tumor nests at the tumor–immunocyte interface, comprising < 5% of tumor cells, and were almost always associated with PD-L1-positive immunocytes. In contrast, tumors with constitutive PD-L1 expression had a higher percentage of positive tumor cells, often diffusely distributed throughout the tumor, and often were not accompanied by PD-L1-positive immunocytes. We propose that distinguishing these two biologically distinctive patterns of PD-L1 expression and typing metastatic instead of primary lesions might better predict immunotherapeutic response to anti-PD1/PD-L1 regimens beyond just the percentage of PD-L1-positive tumor cells.
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Topics {✒️}

anti-pd1/pd-l1 regimens cd274/pd-l1 gene amplification anti-pd-1/pd-l1 agents month download article/chapter small-cell lung cancer pd-l1-positive tumors showed pd-l1-positive scchn showed pd-l1-positive tumor cells recurrent squamous-cell carcinoma pd-l1 immunohistochemistry assays harmonized pd-l1 immunohistochemistry constitutive pd-l1 expression squamous cell carcinoma pd-l1 protein expression defining pd-l1 expression membranous pd-l1 expression squamous cell cancer pd-l1-positive immunocytes pd-1-expressing tumor-infiltrating b7-h1 expression model advanced squamous-cell pulmonary squamous-cell human papillomavirus-negative head human papillomavirus-positive full article pdf pd-l1-positive related subjects pd-l1 expression pd-l1 pathway neck cancer patients privacy choices/manage cookies article scognamiglio theresa scognamiglio positive tumor cells nat rev cancer b7-h1 expression nivolumab versus docetaxel tumor-infiltrating immunocytes lung cancer tumor–immunocyte interface european economic area neck pathology aims phase 1b trial phase ii study programmed death-1 ethics declarations conflict pd-l1 tumor immune microenvironment objective response rates predict immunotherapeutic response

Questions {❓}

Cancer treatment with Anti-PD-1/PD-L1 agents: is PD-L1 expression a biomarker for patient selection?

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         description:Anti-PD1 antibody has been approved for metastatic squamous cell carcinoma of the head and neck (SCCHN) and objective response rates of approximately 20% have been reported. Defining PD-L1 expression at ≥ 1% tumor cells as positive, PD-L1-positive tumors showed a higher response rate. However, it is unclear whether 1% is the optimal cutoff, and studies on lung cancer suggested 50% cutoff as a stronger predictive biomarker. 96 primary SCCHN from oropharynx and oral cavity and 34 corresponding metastatic lesions were typed for membranous PD-L1 expression. p16 immunohistochemistry was used as a surrogate marker for HPV status in SCCHN from the oropharynx. Fifty-two of 96 (54%) tumors were PD-L1-positive, 72% if PD-L1 expression in tumor-infiltrating immunocytes was also included as positive. Fifteen of 34 primary-metastasis tumor pairs differed in PD-L1 expression, and p16(+) cases more frequently showed PD-L1 expression in immunocytes than p16(−) cases (82 vs. 45%, p < 0.05). PD-L1-positive SCCHN showed two distinct patterns of expression. In the induced pattern of expression, PD-L1-positive tumor cells were limited to the periphery of tumor nests at the tumor–immunocyte interface, comprising < 5% of tumor cells, and were almost always associated with PD-L1-positive immunocytes. In contrast, tumors with constitutive PD-L1 expression had a higher percentage of positive tumor cells, often diffusely distributed throughout the tumor, and often were not accompanied by PD-L1-positive immunocytes. We propose that distinguishing these two biologically distinctive patterns of PD-L1 expression and typing metastatic instead of primary lesions might better predict immunotherapeutic response to anti-PD1/PD-L1 regimens beyond just the percentage of PD-L1-positive tumor cells.
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