Epithelial-to-mesenchymal transition and autophagy induction in breast carcinoma promote escape from t-cell-mediated lysis

Intissar Akalay, Bassam Janji, Meriem Hasmim, Muhammad Zaeem Noman, Fabrice André, Patricia De Cremoux, Philippe Bertheau, Cécile Badoual, Philippe Vielh, Annette K. Larsen, Michele Sabbah, Tuan Zea Tan, Joan Herr Keira, Nicole Tsang Ying Hung, Jean Paul Thiery, Fathia Mami-Chouaib, Salem Chouaib*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

215 Citations (Scopus)

Abstract

Epithelial-to-mesenchymal transition (EMT) mediates cancer cell invasion, metastasis, and drug resistance, but its impact on immune surveillance has not been explored. In this study, we investigated the functional consequences of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes (CTL). Acquisition of the EMT phenotype in various derivatives of MCF-7 human breast cancer cells was associated with dramatic morphologic changes and actin cytoskeleton remodeling, with CD24-/CD44 +/ALDH+ stem cell populations present exhibiting a higher degree of EMT relative to parental cells. Strikingly, acquisition of this phenotype also associated with an inhibition of CTL-mediated tumor cell lysis. Resistant cells exhibited attenuation in the formation of an immunologic synapse with CTLs along with the induction of autophagy in the target cells. This response was critical for susceptibility to CTL-mediated lysis because siRNA-mediated silencing of beclin1 to inhibit autophagy in target cells restored their susceptibility to CTL-induced lysis. Our results argue that in addition to promoting invasion and metastasis EMT also profoundly alters the susceptibility of cancer cells to T-cell-mediated immune surveillance. Furthermore, they reveal EMT and autophagy as conceptual realms for immunotherapeutic strategies to block immune escape. Cancer Res; 73(8); 2418-27.

Original languageEnglish
Pages (from-to)2418-2427
Number of pages10
JournalCancer Research
Volume73
Issue number8
DOIs
Publication statusPublished - 15 Apr 2013

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