The goal of this study was to determine whether antiIL-6Rα block (tocilizumab) will alter the pleural secretome and will diminish tumor-specific immune responses.

Pleural T cells were isolated from freshly drained pleural effusions (n=6). Autologous pleural tumor was expanded in vitro using the Mammary Epithelial Growth Medium (Lonza). Pleural T cells were stimulated using anti-CD3/CD28 Dynal beads and low dose IL-2 (60 Cetus U/ml) for 2,4,7, 14 or 21 days in the presence of tocilizumab for the last 48h (0, 0.35, 0.72, 1.43, 2.86 and 5.72ug/ml). Pleural T cell effectors were counted and plated on tumor targets at 12.5:1 E:T in the presence of tocilizumab.

Ex vivo expanded pleural T cells were effector-memory phenotype (CD45RA-CD27-) and were highly cytotoxic against autologous tumor (89-100%). The majority of CD8+ T cells were central memory (CD45RA-/CD27-) or effector memory (CD45RA+/CD27-); the majority co-expressed granzyme B, perforin, 20-60% expressed PD-1. Most CD4+ co-expressed granzyme B and perforin and were PD-1+, suggesting cytotoxic CD4+ T cells. The presence of tocilizumab reversed tumor EMT but did not alter cytotoxicity.

We show that the IL-6/IL-6Rα axis is prominent in MPE, drives tumor growth and inhibits anti-tumor immunity. Pleural T cells are neither exhausted nor dysfunctional but are suppressed by the pleural environment. Ex vivo expanded MPE CD8 and CD4 T cells are highly cytotoxic against autologous tumor. Anti-IL-6Rα block reverses tumor EMT but does not inhibit effector responses.