Distinct immune status in patients with adenocarcinoma and squamous cell carcinoma: implication for immunotherapy of non-small cell lung cancer

Irena Adkins^1,2, Nada Hradilova^1,2, Ondrej Palata^1,2 Lenka Palova Jelinkova^1,2, Klara Danova^1,2, Michal Hensler¹, Lenka Sadilkova¹, Dagmar Mysikova³, Robert Lischke³, Radek Spisek^1,2
¹SOTIO a.s, Prague, Czech Republic; ²Department of Immunology, 2^nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic; ³ Thoracic and Lung Transplantation Division, 3^rdDepartment of Surgery, 1^st Faculty of Medicine, Charles University in Prague and University Hospital Motol

Lung cancer is the leading cause of cancer mortality worldwide therefore understanding the role of the immune system in antitumor immunity is of a great interest. Here we compared immune cell infiltration and responses in tumors and non-tumoral lung tissue from 43 adenocarcinomas (AC) and 39 squamous cell carcinomas (SCC) of neoadjuvant non-small cell lung cancer patients. We compared infiltration and function of T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSC) in tumors as well as in blood of these patients. Whereas T, B and NK cells infiltration was comparable in AC and SCC, the number of dendritic cells was lower in SCC tumors. CD8⁺ T cell and NK cell proliferation, IFN-γ-production from T cells and secretion of proinflammatory cytokines after stimulation in vitro was lower in SCC compared to AC tumors. A higher number of Tregs was detected in tumors and blood of AC patients, whereas a higher number of MDSC was found in SCC patients. The suppressive function of Tregs was comparable between AC and SCC patients, but MDSC in SCC patients displayed a higher suppressive function as shown by inhibition of CD3 expression and IL-2 and IFN-γ production in T cells, increased Arg1 expression and Lox-1 plasma concentrations compared to AC patients and age-matched controls. Our results suggest that immune system of SCC patients might be subjected to higher immunosuppression than AC patients. Our observations also give rationale to target specifically MDSC in SCC patients and Tregs in AC patients for designing combinatorial immunotherapeutic approaches.

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