Single-cell sequencing reveals effects of chemotherapy on the immune landscape and TCR/BCR clonal expansion in a relapsed ovarian cancer patient

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.

Screening of Prognostic Molecular Markers and Establishment of Prognostic Model for G-protein Coupled Receptor-Related Genes in Epithelial Ovarian Serous Cancer Based on Machine Learning Method

“…Other study [57] 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. There are also study [58]by others that suggest that suppression of ovarian cancer metastasis can be achieved by targeting MDSC in ltration in TME through disrupting LncOVM-PPIP5K2-complement axis, providing an option for treating ovarian cancer patients.We therefore suggest that there is a positive correlation between our screened GPCRRGs and the in ltration abundance of the majority of immune cells, which might be strongly linked to the immune microenvironment thereby in uencing ovarian cancer development.…”

Altered tumor signature and T‐cell profile after chemotherapy reveal new therapeutic opportunities in high‐grade serous ovarian carcinoma

“…In contrast, unique T‐cell clones dominated the post‐treatment tissues ( p = 0.031). Interestingly, previous reports have indicated a decrease in highly expanded T‐cell clones in PBMC samples from a patient with HGSOC after chemotherapy, 36 suggesting a systemic depletion of dividing T cells.…”

Identification of peripheral blood immune infiltration signatures and construction of monocyte-associated signatures in ovarian cancer and Alzheimer's disease using single-cell sequencing

“…The subsequent prognostic models were constructed using a total of 376 patients from the TCGA cohort, 285 patients from the GSE989 cohort, and 101 patients from the GSE63885 cohort. Additionally, we obtained 10× single-cell RNA sequencing data from two peripheral blood samples of OC patients from GSE213243 [ 22 ]. A cohort comprising 20 healthy controls and 48 ovarian cancer patients was sourced from GSE31682 [ 23 ].…”