Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma

Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma

Marius Ilié;Mélanie Beaulande;Saima Ben Hadj;Emmanuel Chamorey;Renaud Schiappa;Elodie Long-Mira;Sandra Lassalle;Catherine Butori;Charlotte Cohen;Sylvie Leroy;Olivier Guérin;Jérôme Mouroux;Charles-Hugo Marquette;Jean-François Pomerol;Gilles Erb;Véronique Hofman;Paul Hofman;Ilié, Marius;Beaulande, Mélanie;Ben Hadj, Saima;Chamorey, Emmanuel;Schiappa, Renaud;Long-Mira, Elodie;Lassalle, Sandra;Butori, Catherine;Cohen, Charlotte;Leroy, Sylvie;Guérin, Olivier;Mouroux, Jérôme;Marquette, Charles-Hugo;Pomerol, Jean-François;Erb, Gilles;Hofman, Véronique;Hofman, Paul;
Cancers 2018 Vol. 10 pp. 326-
193
ilié2018cancerschromogenic

Abstract

With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quantification. The CD4+/CD8+ ratio was significantly higher in elderly patients. In patients <75 years, the density of CD4+, CD8+, and PD-L1 in TAICs showed a positive significant correlation with PD-L1 expression in tumor cells (TCs), while a lower correlation was observed in the elderly population. In the latter, a high CD4+/CD8+ ratio, and combined PD-L1 expression ≥1% TCs with a low CD8+ density, low CD33+ density, and a high CD4+ density correlated to worse overall survival. We identified differences according to age in the CD4+/CD8+ ratio and in correlation between PD-L1 expression and the density of TAICs in LADC patients. Distinct groups of tumor microenvironments had an impact on the OS of elderly patients with LADC.

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