Abstract 5134: Evaluation of immune tolerance mechanisms in pulmonary squamous cell and adenocarcinomas - how to interfere beyond PDL1 blockade

Abstract

Abstract Introduction: Immunotherapy has emerged as a new tool to treat patients with NSCLC. Programmed death ligand 1 (PDL1) expressed on carcinoma cells serve as a marker predicting the response of anti-PDL antibody therapy. However, the results of clinical studies are conflicting as patients might profit from therapy despite not expressing PDL1 on their tumors, and also some tumors expressing PDL1 do not respond to therapy. It is evident that NSCLC cells use other mechanisms of immunotolerance. Methods: Surgically removed specimen of lung cancer are evaluated for infiltrating innate as well as specific immune cell in tumor centers and invasive front. In addition bronchoalveolar lavage is taken simultaneously and evaluated by flow cytometry for the same immune cells as the tissues. These cell types are evaluated: dendritic cells (classical, plasmocytoid, monocytoid), macrophages (M1 and M2), lymphocytes of Bcell lineage, lymphocytes of Tcell lineage, regulatory Tcells, natural killer cells. In addition tumor cells and lymphocytes are studied for their expression of PD1, PDL1, and PDL2, respectively Results and discussion: Within lung cancer several different mechanisms of inducing immune tolerance emerged: PD1-PDL1 interaction of tumor cells and CD8 lymphocytes, plasmocytoid as well as monocytoid dendritic cell induced downregulation of cytotoxic Tcell action, influx of myeloid derived cells inducing immune tolerance against tumor cells, M2 macrophage polarization with enhancement of stroma remodeling for tumor cell invasion and reduced Tcell reaction, increase of Treg cells inducing immune tolerance. Some of these mechanisms are seen in combination with PD1-PDL1 induced immune tolerance. This might explain, why some patients do not benefit from anti-PDL1 therapy. BAL emerged as a powerful tool in the evaluation of the immune reaction in NSCLC patients and might be a tool for evaluation of immune responses as well as a diagnostic tool to evaluate resistance mechanisms. Citation Format: Helmut H. Popper, Luka Brcic, Gudrun Absenger, Barbara Prietl, Joerg Lindenmann, Marija Balic. Evaluation of immune tolerance mechanisms in pulmonary squamous cell and adenocarcinomas - how to interfere beyond PDL1 blockade. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5134.