Abstract B092: Tumor infiltrating T-cells from renal cell carcinoma patients recognize neoantigens derived from point and frameshift mutations

Abstract

Mutation-derived neoantigens are important targets of T-cell mediated reactivity towards tumors. Their unique tumor-restriction poses an advantage compared to shared tumor antigens in that they are in principle both foreign and tumor specific, hence presumably less impacted by T-cell tolerance and for therapeutic applications less prone to mediate immune-related destruction of noncancerous tissue. Moreover, the mutational burden and predicted number of neoantigens correlate to favorable clinical outcome and benefit from immune checkpoint therapy. Neoantigen-reactive T-cells have been detected across a number of solid cancers, ranging from immunogenic tumors such as melanoma and non-small cell lung cancer to less immunogenic tumors such as breast cancer. Renal cell carcinomas (RCCs) are among medium-range mutational burden tumors and present with the highest pan-cancer number and proportion of frameshift mutations, a mutation type considered to be highly immunogenic. However, to our knowledge, yet no reports have described neoantigen-specific T-cells in this malignancy. In this study, the mutational landscape and HLA (human leukocyte antigen) profile of tumors from six renal cell carcinoma patients were analyzed by whole-exome sequencing (WXS) of DNA from tumor fragments (TFs), autologous tumor cell lines (TCLs) and tumor-infiltrating lymphocytes (TILs, germline reference). Hereafter the online MuPeXi tool was used to predict binding of mutated peptide sequences of 9-11mer length to the HLAs of each patient, using a rank score Citation Format: Sofie Ramskov, Ulla Kring Hansen, Anne-Mette Bjerregaard, Amalie Kai Bentzen, Marco Donia, Rikke Andersen, Zoltan Szallasi, Inge Marie Stentoft Svane, Aron Charles Eklund, Sine Reker Hadrup. Tumor infiltrating T-cells from renal cell carcinoma patients recognize neoantigens derived from point and frameshift mutations [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B092.