AUTHOR=Ren Yanyu , Li Runrong , Feng Hanxiao , Xie Jieying , Gao Lin , Chu Shuai , Li Yan , Meng Fanliang , Ning Yunshan TITLE=Single-cell sequencing reveals effects of chemotherapy on the immune landscape and TCR/BCR clonal expansion in a relapsed ovarian cancer patient JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.985187 DOI=10.3389/fimmu.2022.985187 ISSN=1664-3224 ABSTRACT=

Cancer recurrence and chemoresistance are the leading causes of death in high-grade serous ovarian cancer (HGSOC) patients. However, the unique role of the immune environment in tumor progression for relapsed chemo-resistant patients remains elusive. In single-cell resolution, we characterized a comprehensive multi-dimensional cellular and immunological atlas from tumor, ascites, and peripheral blood of a chemo-resistant patient at different stages of treatment. Our results highlight a role in recurrence and chemoresistance of the immunosuppressive microenvironment in ascites, including MDSC-like myeloid and hypo-metabolic γδT cells, and of peripheral CD8+ effector T cells with chemotherapy-induced senescent/exhaustive. Importantly, paired TCR/BCR sequencing demonstrated relative conservation of TCR clonal expansion in hyper-expanded CD8+ T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy. Thus, our study suggests strategies for ameliorating chemotherapy-induced immune impairment to improve the clinical outcome of HGSOC.