Synapse - Programme of self-reactive innate-like T cell-mediated cancer immunity

Programme of self-reactive innate-like T cell-mediated cancer immunity Journal Article

Authors:	Chou, C.; Zhang, X.; Krishna, C.; Nixon, B. G.; Dadi, S.; Capistrano, K. J.; Kansler, E. R.; Steele, M.; Han, J.; Shyu, A.; Zhang, J.; Stamatiades, E. G.; Liu, M.; Li, S.; Do, M. H.; Edwards, C.; Kang, D.; Chen, C. T.; Wei, I. H.; Pappou, E. P.; Weiser, M. R.; Garcia-Aguilar, J.; Smith, J. J.; Leslie, C. S.; Li, M. O.
Article Title:	Programme of self-reactive innate-like T cell-mediated cancer immunity
Abstract:	Cellular transformation induces phenotypically diverse populations of tumour-infiltrating T cells(1-5), and immune checkpoint blockade therapies preferentially target T cells that recognize cancer cell neoantigens(6,7). Yet, how other classes of tumour-infiltrating T cells contribute to cancer immunosurveillance remains elusive. Here, in a survey of T cells in mouse and human malignancies, we identified a population of alpha beta T cell receptor (TCR)-positive FCER1G-expressing innate-like T cells with high cytotoxic potential8 (ILTCKs). These cells were broadly reactive to unmutated self-antigens, arose from distinct thymic progenitors following early encounter with cognate antigens, and were continuously replenished by thymic progenitors during tumour progression. Notably, expansion and effector differentiation of intratumoural ILTCKs depended on interleukin-15 (IL-15) expression in cancer cells, and inducible activation of IL-15 signalling in adoptively transferred ILTCK progenitors suppressed tumour growth. Thus, the antigen receptor self-reactivity, unique ontogeny, and distinct cancer cell-sensing mechanism distinguish ILTCKs from conventional cytotoxic T cells, and define a new class of tumour-elicited immune response.
Keywords:	antigen; receptor; precursor; reveals; mechanism; fate; selection; origin; lymphoid-cells
Journal Title:	Nature
Volume:	605
Issue:	7908
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Date Published:	2022-05-05
Start Page:	139
End Page:	145
Language:	English
ACCESSION:	WOS:000784934100006
DOI:	10.1038/s41586-022-04632-1
PROVIDER:	wos
PUBMED:	35444279
PMCID:	PMC9250102
Notes:	Article -- Source: Wos