Abstract B79: Identification and analysis of tumor-reactive CTLs in ovarian and cervical cancer tissues for developing a personalized immunotherapy

Cancer immunotherapy that target individual mutated neoantigens can mediate tumor regression. Ovarian cancer and cervical cancer are known to have relatively many somatic mutations and are considered to be good indications for immunotherapy. In order to develop personalized immunotherapy, we aimed to clarify the mutated neoantigens of individual patients with these cancers and to characterize the tumor antigen specific CTLs infiltrating into the tumor tissues. We obtained resected tumor tissues and normal tissues from about 30 patients with ovarian cancer or cervical cancer. In ex vivo assay, we investigated the cell surface markers of CD8 + T cell in tumor and normal tissues and identified that the expression of CD107a or co-inhibitory molecules on CD8 + T cells in tumor tissues was higher than that in normal tissues. These tumor-infiltrating lymphocytes were cultured for 14 days and we could expand the numbers of TILs from all patients’ tumors. At the same time, we tried to establish patient derived xenografts (PDX) mouse model or generate tumor cell lines from these patients. In cases where we could obtain tumor cells by these ways, TILs and autologous tumor cells were co-cultured and we evaluated the tumor reactive CTLs by CD107a assay. Tumor reactive CTLs were enriched by sorting for CD107a + PD-1 + CD8 + T cells and expanded in vitro. The expanded CD 107a + PD-1 + CD8 + T cells were co-cultured with autologous tumor cells and expression of CD 107a was analyzed. As a result, the proportion of CD 107a + cells increased after expansion. Therefore, we could prove that many tumor-reactive CTLs are contained in population of CD107a + PD-1 + CD8 + T cells. These results may provide the marker to isolate tumor reactive TILs ex vivo. We will identify candidates of mutated neoantigens by the next generation sequencing combined with bioinformatics prediction and will find the tumor reactive CTLs and these TCRs that recognize these mutated neoantigens. Citation Format: Kazuto Nosaka, Yoshiaki Yoshikawa, Toshihiro Suzuki, Keigo Saito, Manami Shimomura, Shoichi Mizuno, Shiro Suzuki, Fumitaka Kikkawa, Tetsuya Nakatsura. Identification and analysis of tumor-reactive CTLs in ovarian and cervical cancer tissues for developing a personalized immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B79.