Journal article

IRF4 instructs effector Treg differentiation and immune suppression in human cancer

Giorgia Alvisi, Jolanda Brummelman, Simone Puccio, Emilia MC Mazza, Elisa Paoluzzi Tomada, Agnese Losurdo, Veronica Zanon, Clelia Peano, Federico S Colombo, Alice Scarpa, Marco Alloisio, Ajithkumar Vasanthakumar, Rahul Roychoudhuri, Marinos Kallikourdis, Massimiliano Pagani, Egesta Lopci, Pierluigi Novellis, Jonas Blume, Axel Kallies, Giulia Veronesi Show all

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2020

Abstract

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, direc..

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Grants

Awarded by Associazione Italiana per la Ricerca sul Cancro


Awarded by Bristol-Myers Squibb


Awarded by Italian Ministry of Health


Funding Acknowledgements

We wish to thank Elisa Dieci (Humanitas Clinical and Research Center) for helping with patients' information, Gianluca Rotta and Jens Fleischer (BD Biosciences) for helping with FACSymphony A5 instrument setup, as well as Silvia Piconese (University of Rome La Sapienza), Gioacchino Natoli (European Institute of Oncology), and the members of the Laboratory of Translational Immunology for critical discussion. This work has been supported by grants from the Associazione Italiana per la Ricerca sul Cancro (investigator grant 20676 to E. Lugli and My First AIRC Grant 189323 to E. Lopci), Bristol-Myers Squibb (preclinical grant CA209-9YM to E. Lugli), and the Humanitas Clinical and Research Center. J. Brummelman is a recipient of the "Fondo di beneficenza Intesa San Paolo" fellowship from AIRC. EMCM and PN are recipients of the 2017 Fondazione Umberto Veronesi postdoctoral fellowship. Purchase of the BD FACSymphony A5 has been in part defrayed by a grant from Italian Ministry of Health (agreement 82/2015). AK is supported by grants and a fellowship from the National Health and Medical Research Council of Australia. J. Blume was supported by a fellowship from the Deutsche Forschungsgemeinschaft.