Enriched circulating and tumor-resident TGF-ß+ regulatory B cells in patients with melanoma promote FOXP3+ Tregs.
Oncoimmunology
; 11(1): 2104426, 2022.
Article
em En
| MEDLINE
| ID: mdl-35909944
ABSTRACT
B cells are emerging as key players of anti-tumor adaptive immune responses. We investigated regulatory and pro-inflammatory cytokine-expressing B cells in patients with melanoma by flow cytometric intracellular cytokine, CyTOF, transcriptomic, immunofluorescence, single-cell RNA-seq, and BT cell co-culture analyses. We found enhanced circulating regulatory (TGF-ß+ and PD-L1+) and reduced pro-inflammatory TNF-α+ B cell populations in patients compared with healthy volunteers (HVs), including lower IFN-γ+IL-4+ and higher TGF-ß+TNF-α+ B cell ratios in patients. TGF-ß-expressing B cells in the melanoma tumor microenvironment assembled in clusters and interacted with T cells via lymphoid recruitment (SELL, CXCL13, CCL4, CD74) signals and with Tregs via CD47SIRP-γ, and FOXP3-promoting Galectin-9CD44. While reduced in tumors compared to blood, TNF-α-expressing B cells engaged in crosstalk with Tregs via TNF-α signaling and the ICOS/ICOSL axis. Patient-derived B cells promoted FOXP3+ Treg differentiation in a TGF-ß-dependent manner, while sustaining expression of IFN-γ and TNF-α by autologous T-helper cells and promoting T-helper cell proliferation ex vivo, an effect further enhanced with anti-PD-1 checkpoint blockade. Our findings reveal cytokine-expressing B cell compartments skewed toward regulatory phenotypes in patient circulation and melanoma lesions, intratumor spatial localization, and bidirectional crosstalk between B and T cell subsets with immunosuppressive attributes.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Linfócitos T Reguladores
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Linfócitos B Reguladores
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Melanoma
Limite:
Humans
Idioma:
En
Revista:
Oncoimmunology
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido