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

Chun Chou, Xian Zhang, Chirag Krishna, Briana G. Nixon, Saida Dadi, Kristelle J. Capistrano, Emily R. Kansler, Miranda Steele, Jian Han, Amy Shyu, Jing Zhang, Efstathios G. Stamatiades, Ming Liu, Shun Li, Mytrang H. Do, Chaucie Edwards, Davina S. Kang, Chin-Tung Chen, Iris H. Wei, Emmanouil P. Pappou, Martin R. Weiser, J. Garcia-Aguilar, J. Joshua Smith, Christina S. Leslie and Ming O. Li ()
Additional contact information
Chun Chou: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Xian Zhang: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Chirag Krishna: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Briana G. Nixon: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Saida Dadi: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Kristelle J. Capistrano: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Emily R. Kansler: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Miranda Steele: iRepertoire
Jian Han: iRepertoire
Amy Shyu: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Jing Zhang: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Efstathios G. Stamatiades: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Ming Liu: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Shun Li: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Mytrang H. Do: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Chaucie Edwards: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Davina S. Kang: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Chin-Tung Chen: Memorial Sloan Kettering Cancer Center
Iris H. Wei: Memorial Sloan Kettering Cancer Center
Emmanouil P. Pappou: Memorial Sloan Kettering Cancer Center
Martin R. Weiser: Memorial Sloan Kettering Cancer Center
J. Garcia-Aguilar: Memorial Sloan Kettering Cancer Center
J. Joshua Smith: Memorial Sloan Kettering Cancer Center
Christina S. Leslie: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Ming O. Li: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center

Nature, 2022, vol. 605, issue 7908, 139-145

Abstract: Abstract Cellular transformation induces phenotypically diverse populations of tumour-infiltrating T cells1–5, and immune checkpoint blockade therapies preferentially target T cells that recognize cancer cell neoantigens6,7. 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 αβ 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.

Date: 2022
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DOI: 10.1038/s41586-022-04632-1

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