CD8+ T-cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation.
Eur J Immunol
; 45(1): 71-81, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25310972
ABSTRACT
Increasing evidence suggests that premetastatic niches, consisting mainly of myeloid cells, provide microenvironment critical for cancer cell recruitment and survival to facilitate metastasis. While CD8(+) T cells exert immunosurveillance in primary human tumors, whether they can exert similar effects on myeloid cells in the premetastatic environment is unknown. Here, we show that CD8(+) T cells are capable of constraining premetastatic myeloid cell accumulation by inducing myeloid cell apoptosis in C57BL/6 mice. Ag-specific CD8(+) T-cell cytotoxicity against myeloid cells in premetastatic lymph nodes is compromised by Stat3. We demonstrate here that Stat3 ablation in myeloid cells leads to CD8(+) T-cell activation and increased levels of IFN-γ and granzyme B in the premetastatic environment. Furthermore, Stat3 negatively regulates soluble Ag cross-presentation by myeloid cells to CD8(+) T cells in the premetastatic niche. Importantly, in tumor-free lymph nodes of melanoma patients, infiltration of activated CD8(+) T cells inversely correlates with STAT3 activity, which is associated with a decrease in number of myeloid cells. Our study suggested a novel role for CD8(+) T cells in constraining myeloid cell activity through direct killing in the premetastatic environment, and the therapeutic potential by targeting Stat3 in myeloid cells to improve CD8(+) T-cell immunosurveillance against metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Melanoma Experimental
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Linfócitos T Citotóxicos
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Regulação Neoplásica da Expressão Gênica
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Macrófagos Peritoneais
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Vigilância Imunológica
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos