Induction of anergic or regulatory tumor-specific CD4+ T cells in the tumor-draining lymph node

Ruby Alonso, Héloïse Flament, Sébastien Lemoine, Christine Sedlik, Emanuel Bottasso, Isabel Péguillet, Virginie Prémel, Jordan Denizeau, Marion Salou, Aurélie Darbois, Nicolás Gonzalo Núñez, Benoit Salomon, David Gross, Eliane Piaggio and Olivier Lantz ()
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Ruby Alonso: PSL University, Institut Curie
Héloïse Flament: PSL University, Institut Curie
Sébastien Lemoine: Institut Necker Enfants Malades
Christine Sedlik: PSL University, Institut Curie
Emanuel Bottasso: PSL University, Institut Curie
Isabel Péguillet: Laboratoire d’immunologie clinique, Institut Curie
Virginie Prémel: PSL University, Institut Curie
Jordan Denizeau: PSL University, Institut Curie
Marion Salou: PSL University, Institut Curie
Aurélie Darbois: PSL University, Institut Curie
Nicolás Gonzalo Núñez: PSL University, Institut Curie
Benoit Salomon: Centre d’Immunologie et des Maladies Infectieuses (CIMI)
David Gross: Institut Necker Enfants Malades
Eliane Piaggio: PSL University, Institut Curie
Olivier Lantz: PSL University, Institut Curie

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract CD4+ T cell antitumor responses have mostly been studied in transplanted tumors expressing secreted model antigens (Ags), while most mutated proteins in human cancers are not secreted. The fate of Ag-specific CD4+ T cells recognizing a cytoplasmic Ag in mice bearing autochthonous tumors is still unclear. Here we show, using a genetically engineered lung adenocarcinoma mouse model, that naive tumor-specific CD4+ T cells are activated and proliferate in the tumor-draining lymph node (TdLN) but do not differentiate into effectors or accumulate in tumors. Instead, these CD4+ T cells are driven toward anergy or peripherally-induced Treg (pTreg) differentiation, from the early stage of tumor development. This bias toward immune suppression is restricted to the TdLN, and is maintained by Tregs enriched in the tumor Ag-specific cell population. Thus, tumors may enforce a dominant inhibition of the anti-tumor CD4 response in the TdLN by recapitulating peripheral self-tolerance mechanisms.

Date: 2018
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DOI: 10.1038/s41467-018-04524-x

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