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• W2980933209 abstract "Abstract Purpose: Programmed death ligand 1 (PD-L1) is expressed in tumor cells and immune cells, and both have been associated with response to anti-PD-1 axis immunotherapy. Here, we examine the expression of PD-L1 to determine which cell type carries the predictive value of the test. Experimental Design: We measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts (425 nonimmunotherapy-treated cases and 62 pembrolizumab/nivolumab/atezolizumab-treated cases). The PD-L1 level was selectively measured in different immune cell subsets using two multiplexed quantitative immunofluorescence panels, including CD56 for natural killer cells, CD68 for macrophages, and CD8 for cytotoxic T cells. Results: PD-L1 was significantly higher in macrophages in both tumor and stromal compartment compared with other immune cells. Elevated PD-L1 in macrophages was correlated with high PD-L1 level in tumor as well as CD8 and CD68 level (P &lt; 0.0001). High PD-L1 expression in macrophages was correlated with better overall survival (OS; P = 0.036 by cell count/P = 0.019 by molecular colocalization), while high PD-L1 expression in tumor cells was not. Conclusions: In nearly 500 non–small cell lung cancer (NSCLC) cases, the predominant immune cell type that expresses PD-L1 is CD68+ macrophages. The level of PD-L1 in macrophages is significantly associated with the level of PD-L1 in tumor cells and infiltration by CD8+ T cells, suggesting a connection between high PD-L1 and “hot” tumors. In anti-PD-1 axis therapy–treated patients, high levels of PD-L1 expression in macrophages are associated with longer OS and may be responsible for the predictive effect of the marker." @default.
• W2980933209 created "2019-10-25" @default.
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• W2980933209 date "2020-02-14" @default.
• W2980933209 modified "2023-10-16" @default.
• W2980933209 title "Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy" @default.
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• W2980933209 doi "https://doi.org/10.1158/1078-0432.ccr-19-1040" @default.
• W2980933209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7024671" @default.
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