American Association for Cancer Research
10780432ccr191040-sup-219781_4_supp_5809028_pytffg.pdf (363.79 kB)

Supplementary Data from Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy

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journal contribution
posted on 2023-03-31, 21:26 authored by Yuting Liu, Jon Zugazagoitia, Fahad Shabbir Ahmed, Brian S. Henick, Scott N. Gettinger, Roy S. Herbst, Kurt A. Schalper, David L. Rimm

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Yale SPORE in Lung Cancer



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. 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. 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 < 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. 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.

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