In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-11)
Abstract:
As the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells’ roles in the anti-tumor response are far from clear. Methods Based on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [B IR (ICI-Responsive B) cells] and described the phenotype, cell–cell communication, biological processes, gene signature, and prognosis value of B IR cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation. Results B IR cells were identified as a subset of CD20 + CD22 + ADAM28 + B cells with a memory phenotype. Bioinformatic analysis revealed that B IR cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of B IR cells. Immunofluorescence confirmed the presence of B IR cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. B IR -associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and B IR -cell density predicted NSCLC patients’ response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of B IR cells were resistant to ICIs. Conclusions CD20 + CD22 + ADAM28 + B IR cells were present in cancer-associated TLS and promoted the response to ICI therapy.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.865596
DOI:
10.3389/fimmu.2022.865596.s001
DOI:
10.3389/fimmu.2022.865596.s002
DOI:
10.3389/fimmu.2022.865596.s003
DOI:
10.3389/fimmu.2022.865596.s004
DOI:
10.3389/fimmu.2022.865596.s005
DOI:
10.3389/fimmu.2022.865596.s006
DOI:
10.3389/fimmu.2022.865596.s007
DOI:
10.3389/fimmu.2022.865596.s008
DOI:
10.3389/fimmu.2022.865596.s009
DOI:
10.3389/fimmu.2022.865596.s010
DOI:
10.3389/fimmu.2022.865596.s011
DOI:
10.3389/fimmu.2022.865596.s012
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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