Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer.
Cancer Cell
; 39(7): 928-944.e6, 2021 07 12.
Article
em En
| MEDLINE
| ID: mdl-33961783
ABSTRACT
Distinct T cell infiltration patterns, i.e., immune infiltrated, excluded, and desert, result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these tumor immune phenotypes remain elusive. Here, we provide a high-resolution dissection of the entire tumor ecosystem through single-cell RNA-sequencing analysis of 15 ovarian tumors. Immune-desert tumors are characterized by unique tumor cell-intrinsic features, including metabolic pathways and low antigen presentation, and an enrichment of monocytes and immature macrophages. Immune-infiltrated and -excluded tumors differ markedly in their T cell composition and fibroblast subsets. Furthermore, our study reveals chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumor cell-T cell cross talk via CXCL16-CXCR6 and stromal-immune cell cross talk via CXCL12/14-CXCR4. Our data highlight potential molecular mechanisms that shape the tumor immune phenotypes and may inform therapeutic strategies to improve clinical benefit from cancer immunotherapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Linfócitos T
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Biomarcadores Tumorais
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Células Estromais
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Análise de Célula Única
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Microambiente Tumoral
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Fibroblastos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article