Immunotherapies targeting the programmed cell death protein 1 (PD-1) to PD ligand 1 (PD-L1) checkpoint have improved prognosis in non-small cell lung cancer (NSCLC). PD-1/PD-L1 status has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study sought to assess PD-L1 status and tumor immune-cell infiltration in NSCLC in HIV patients.
Consecutive HIV patients treated for NSCLC between 1996 and 2014 at Tenon hospital (Paris, France) were enrolled. PD-L1 tumor expression was assessed using immunohistochemistry (2 antibodies: L. Chen, clone 5H1 and Cell Signaling, clone E1L3N). Tumor immune cell infiltration was assessed for CD3 (SP7), CD4 (1F6), CD8 (C8/144b), CD20 (L26), CD163 (10D6) and MPO (59A5). The percentage of PD-L1- and immune-positive cells was ≥5%. The score used is the product of intensity (0, 1, 2 or 3) by positive cell percentage. The PD-L1 score was considered positive if >5. PD-L1 status and immune-cell infiltration results were compared to those of 54 NSCLCs from unknown HIV status patients.
In total, 34 HIV-positive patients were evaluated: predominantly men (88.2%) with a median age of 51.1 years and adenocarcinomas (76.5%) with 38.2% stage IV. The median blood CD4 count was 480/µL (86-1120) and 64% exhibited undetectable viral load. The PD-L1 score was higher in HIV-positive patients (E1L3N clone: 0 [0-150] vs. 0 [0-26.7], p = 0.047; 5H1 clone: 0 [0-120] vs.0 [0-26.7] p = 0.66 respectively) whereas PD-L1 expression frequency did not differ between HIV-positive and HIV-undetermined patients (18.7% vs. 9.3% using E1L3N and 10% vs. 5.6% using 5H1, respectively). There was significantly greater CD8, CD20, and CD163 infiltration in the HIV-positive patients (Table).
|HIV-positive (n = 22)||HIV-undetermined (n = 54)||p-value|
These results suggest that HIV–positive patients should feature in clinical trials assessing PD1/PD-L1 checkpoint inhibitors, and this score could be a better tool for the selection of patients that may benefit from immunotherapies.
Clinical trial identification
Legal entity responsible for the study
APHP, Tenon University Hospital, Paris, France
This study received support from “CARDIF AO n°23 automne 2014” and from “Fonds de dotation 2015 Recherche en Santé Respiratoire AO automne 2015”
All authors have declared no conflicts of interest.