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

Nature Communications
Ruby AlonsoOlivier Lantz

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.

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Citations

Apr 27, 2019·Annals of the New York Academy of Sciences·Tijana Martinov, Brian T Fife
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Datasets Mentioned

BETA
GSE113625

Methods Mentioned

BETA
transgenic
FACS
transfection
Assay
X ray
mechanical dissociation
PMA
flow cytometry
electrophoresis

Software Mentioned

GSEA
GraphPad Prism
Living Image
Oligo
Prism
FlowJo
Bioconductor
R
Limma
Qlucore Omics explorer

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