Globally shared TCR repertoires within the tumor-infiltrating lymphocytes of patients with metastatic gynecologic cancer

• Published in: Scientific reports 2023-11, Vol.13 (1), p.20485-20485, Article 20485
• Main Authors: Kim, Taehoon, Lim, Hyeonseob, Jun, Soyeong, Park, Junsik, Lee, Dongin, Lee, Ji Hyun, Lee, Jung-Yun, Bang, Duhee
• Format: Article
• Language: English
• Subjects: 631/114; 631/250; 631/67; 692/308; 692/699; Biopsy; Blood circulation; BRCA1 Protein; BRCA2 Protein; Chemotherapy; Cloning; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrium; Female; Genomics; Heterogeneity; Humanities and Social Sciences; Humans; Immune system; Immunotherapy; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Metastases; Metastasis; multidisciplinary; Ovarian cancer; Ovarian Neoplasms - genetics; Patients; PD-L1 protein; Peripheral blood; Receptors, Antigen, T-Cell - genetics; Science; Science (multidisciplinary); T cell receptors; Tumor cells; Tumor-infiltrating lymphocytes; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-47740-2

Gynecologic cancer, including ovarian cancer and endometrial cancer, is characterized by morphological and molecular heterogeneity. Germline and somatic testing are available for patients to screen for pathogenic variants in genes such as BRCA1/2. Tissue expression levels of immunogenomic markers such as PD-L1 are also being used in clinical research. The basic therapeutic approach to gynecologic cancer combines surgery with chemotherapy. Immunotherapy, while not yet a mainstream treatment for gynecologic cancers, is advancing, with Dostarlimab recently receiving approval as a treatment for endometrial cancer. The goal remains to harness stimulated immune cells in the bloodstream to eradicate multiple metastases, a feat currently deemed challenging in a typical clinical setting. For the discovery of novel immunotherapy-based tumor targets, tumor-infiltrating lymphocytes (TILs) give a key insight on tumor-related immune activities by providing T cell receptor (TCR) sequences. Understanding the TCR repertoires of TILs in metastatic tissues and the circulation is important from an immunotherapy standpoint, as a subset of T cells in the blood have the potential to help kill tumor cells. To explore the relationship between distant tissue biopsy regions and blood circulation, we investigated the TCR beta chain (TCRβ) in bulk tumor and matched blood samples from 39 patients with gynecologic cancer. We found that the TCR clones of TILs at different tumor sites were globally shared within patients and had high overlap with the TCR clones in peripheral blood.