Back to Search
Start Over
CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours.
- Source :
- Nature; Jun2023, Vol. 618 Issue 7967, p1033-1040, 8p
- Publication Year :
- 2023
-
Abstract
- Most clinically applied cancer immunotherapies rely on the ability of CD8<superscript>+</superscript> 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<superscript>+</superscript> effector cells to contribute to antitumour immunity independently of CD8<superscript>+</superscript> 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<superscript>+</superscript> T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8<superscript>+</superscript> T cell targeting. The CD4<superscript>+</superscript> effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II<superscript>+</superscript>CD11c<superscript>+</superscript> antigen-presenting cells. We show that T helper type 1 cell-directed CD4<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8<superscript>+</superscript> T cells and natural killer cells and advance cancer immunotherapies.This article describes a mechanism through which CD4<superscript>+</superscript> T cells can eradicate MHC-deficient tumours that escape direct CD8<superscript>+</superscript> T cell targeting and thereby complement the activity of CD8<superscript>+</superscript> T cells and natural killer cells to advance cancer immunotherapies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 618
- Issue :
- 7967
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 164641729
- Full Text :
- https://doi.org/10.1038/s41586-023-06199-x