The effect of chemotherapy on the tumor immune microenvironment in non-small cell lung cancer (NSCLC): A single-institution retrospective analysis.

Abstract

155 Background: Platinum-doublet chemotherapy (chemo) is routinely used for treatment of early stage and metastatic NSCLC. Immunotherapy is a proven treatment in these patients as well. The presence of tumor infiltrating lymphocytes (TILs) has been shown to be prognostic of this disease; however, the effect of chemo on TILs and the tumor immune microenvironment in NSCLC has not been well studied. We tested the hypothesis that chemo results in a decrease in the presence of TILs in NSCLC. Methods: We retrospectively identified patients treated with neo-adjuvant platinum-doublet chemo who underwent surgical resection from 2007-2015 at the University of Virginia. The specimens were sectioned and IHC stained for CD8, FoxP3, and PD-L1. Two independent investigators assessed a central and a peripheral high power field of tumor for number of CD8 and FoxP3 positive TILs. An independent pathologist assessed tumor cell PD-L1 expression. The nonparametric Wilcoxon Mann Whitney test was used to compare measurements of TILs in chemo-exposed tissue to a control cohort from a database of NSCLC surgical specimens that had not received pre-operative therapy. Results: Of the 17 patients who met eligibility criteria, 11 had sufficient tissue for evaluation. Results are shown in Table 1. There was a significant decrease in CD8 and FoxP3 TILs in both the center and periphery in patients exposed to chemo. There was no difference in PD-L1 expression. Conclusions: These data suggest that platinum-doublet chemo significantly decreases the presence of cytotoxic and regulatory subsets of TILs without effecting PD-L1 expression. This study is limited by the lack of pre-treatment tumor samples to compare pre- and post-treatment TILs in individual patients. Further studies are warranted to evaluate the impact of decreased TILs in the setting of concurrent or sequential immunotherapy treatment with chemo in NSCLC. [Table: see text]