Abstract 4887: DNA repair mutations are associated with mutational burden and T-cell activation signature in lung adenocarcinoma

DNA repair deficiencies have been linked to the generation of immunogenic neo-antigens and increased efficacy of immunotherapies. To determine the impact of mutations in DNA repair genes, specifically those involved in homologous recombination (HR) and mismatch repair (MMR), on infiltrating immune cells in lung adenocarcinoma, we analyzed the expression of “immune metagenes” linked to specific cell types (Angelova et al. 2015) utilizing RNAseq values from TCGA (515 patients, 230 sequenced). Tumors infiltrated by activated CD4 and CD8, all combined T cells, and all combined cell types contained a higher somatic mutation count, while tumors infiltrated by Th17, NK56 bright, and mast cells were linked to lower mutation count (Table 1, * = p Our characterization revealed significant links between DNA repair deficiencies, mutational burden, and tumor infiltration by activated T cells, thereby identifying potential biomarkers to aid in patient selection for immunotherapy. [J.A. and Y.C. contributed equally to this work.] Citation Format: Young Kwang Chae, Jonathan F. Anker, Massimo Cristofanilli, Aparna Kalyan, Jason Kaplan, Sunandana Chandra, Benedito Carneiro, Maria Matsangou, Cesar Santa-Maria, Francis Giles. DNA repair mutations are associated with mutational burden and T-cell activation signature in lung adenocarcinoma. [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 4887.