Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Revista
País de afiliação
Intervalo de ano de publicação
1.
Nature ; 618(7967): 1033-1040, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37316667

RESUMO

Most clinically applied cancer immunotherapies rely on the ability of CD8+ cytolytic T cells to directly recognize and kill tumour cells1-3. These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment4-6. The ability of CD4+ effector cells to contribute to antitumour immunity independently of CD8+ T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified7-10. Here, we describe a mechanism whereby a small number of CD4+ T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting. The CD4+ effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II+CD11c+ antigen-presenting cells. We show that T helper type 1 cell-directed CD4+ T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4+ T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4+ T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8+ T cells and natural killer cells and advance cancer immunotherapies.


Assuntos
Linfócitos T CD4-Positivos , Morte Celular , Imunoterapia , Inflamação , Neoplasias , Microambiente Tumoral , Humanos , Células Apresentadoras de Antígenos/imunologia , Antígeno CD11c/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Morte Celular/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Imunidade Inata , Inflamação/imunologia , Interferons/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Microambiente Tumoral/imunologia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Células Mieloides/imunologia , Células Th1/citologia , Células Th1/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA