4-1BB co-stimulation further enhances anti-PD-1-mediated reinvigoration of exhausted CD39+CD8 T cells from primary and metastatic sites of epithelial ovarian cancers

• DOI: 10.1136/jitc-2020-001650
• Publication Date: 2021-11-12T18:35:43Z
• Authors: Galam Leem; Junsik Park; Minwoo Jeon; Eui-Soon Kim; Sang Wun Kim; Yong Jae Lee; Seong Jin Choi; Baekgyu Choi; Seongyeol Park; Young Seok Ju; Inkyung Jung; Sunghoon Kim; Eui-Cheol Shin; Jung Yun Lee; Su-Hyung Park
• Keywords: Co-stimulation

Background Responses to immunotherapy vary between different cancer types and sites. Here, we aimed investigate features of exhaustion activation in tumor-infiltrating CD8 T cells at both the primary metastatic sites epithelial ovarian cancer. Methods Tumor tissues peripheral blood were obtained from 65 patients with From these samples, isolated lymphocytes (TILs) mononuclear cells. These used for immunophenotype using multicolor flow cytometry, gene expression profile RNA sequencing ex vivo functional restoration assays. Results We found that CD39 + TILs enriched tumor-specific TILs, status was determined by differential programmed cell death protein 1 (PD-1) level. high PD-1 (PD-1 ) exhibited highly tumor-reactive terminally exhausted phenotypes. Notably, showed similar characteristics terms T-cell Among co-stimulatory receptors, 4-1BB exclusively overexpressed especially on cells, 4-1BB-expressing displayed immunophenotypes indicating higher degrees proliferation, less exhaustion, compared not expressing 4-1BB. Importantly, agonistic antibodies further enhanced anti-PD-1-mediated reinvigoration Conclusion Severely a distinctly heterogeneous levels, providing rationale evidence immunotherapies targeting receptor cancers.