Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.985187
Keywords
single-cell sequencing; ovarian cancer; chemotherapy; immune microenvironment; TCR; BCR repertoire; clonal expansion
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Funding
- National Key Research and Development Project of China [2019YFA0903800]
- National Natural Science Foundation of China [81971903]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515010779]
- Nanfang Hospital President's Fund [2019B019]
- Innovative experiment program of college students of Guangdong Province, China [S202012121095, S202112121130, S202112121136, X202212121322]
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This study characterizes the immune environment in tumor progression of relapsed chemo-resistant ovarian cancer patients at single-cell resolution. The immunosuppressive microenvironment in ascites, including myeloid and gamma delta T cells, as well as peripheral CD8(+) T cells with chemotherapy-induced senescence/exhaustion, play important roles in recurrence and chemoresistance. TCR/BCR sequencing demonstrates the 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.
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 gamma delta T 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.
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