Abstract
Abstract Lung cancer is the leading cause of cancer mortality worldwide; therefore, understanding the biologic role of immune cell infiltrates in the tumor microenvironment is of eminent interest. In this study we compared immune cell populations, T-cell responses and secreted cytokines in primary tumors and nontumoral lung tissue from more than 40 adenocarcinomas (AC) and 40 squamous cell carcinomas (SCC) of non-small cell lung cancer (NSCLC) patients undergoing neoadjuvant surgery. Moreover, we compared immune-suppressive populations such as CD4+CD25+Foxp3+ T regulatory cells and myeloid-derived suppressor cells (MDSC) and the expression of immune checkpoint molecules PD-1, TIM3, LAG-3 and CTLA-4 in the blood of these patients. In both tumor subtypes we observed similarly higher infiltration of B cells, memory T cells, dendritic cells, NK cells, monocytes/macrophages, mast cells and CD4+CD25+Foxp3+ T regulatory cells compared to nontumoral tissue. However, immune cells seemed to be suppressed functionally more in SCC than AC as we detected significantly lower IFN-γ-positive T cells and production of proinflammatory cytokines after stimulation. PD-1, TIM3 and LAG-3 expression on T cells in blood and PD-1 on intratumoral CD8+ T cells of SSC patients were significantly elevated compared to AC patients. Similarly, the high number of MDSC, which correlated with Arginase 1 mRNA levels and downregulation of CD3zeta in T cells, was detected only in SCC. These results suggest that immune system of SSC patients might be subjected to a higher systemic and tumor-associated immune suppression than in AC patients. This should be taken into consideration in designing lung cancer immunotherapeutic approaches. Citation Format: Nada Hradilova, Ondrej Palata, Lenka Sadilkova, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins. Distinct immune status in patients with adenocarcinoma and squamous cell carcinoma: Implication for immunotherapy of non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B82.
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