Epithelial-to-mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell–mediated Lysis

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Epithelial-to-mesenchymal transition is known to mediate cancer cell invasion, metastasis, and drug resistance, but its impact on cancer immune surveillance is less well defined. In a study reported in Cancer Research, Akalay and colleagues found that epithelial-to-mesenchymal transition and autophagy induction in breast cancer cells was associated with inhibition of cytotoxic T lymphocyte–mediated tumor cell lysis.

In the study, acquisition of the epithelial-to-mesenchymal transition phenotype in derivatives of MCF-7 human breast cancer cells was associated with marked morphologic changes and actin cytoskeleton remodeling, with the CD24-negative/CD44-positive/ALDH-positive stem cell populations present exhibiting a greater degree of epithelial-to-mesenchymal transition compared with parental cells. Acquisition of the phenotype was also associated with inhibition of cytotoxic T lymphocyte–mediated tumor cell lysis.

The resistant cells exhibited formation of an immunologic synapse with cytotoxic T lymphocytes, accompanied by induction of autophagy in the target cells. This response was found to be critical to modulating susceptibility to cytotoxic T lymphocyte–mediated lysis, with siRNA-mediated silencing of beclin1 to inhibit autophagy in the target cells restoring target cell susceptibility to lysis.

The investigators concluded, “Our results argue that in addition to promoting invasion and metastasis, epithelial-to-mesenchymal transition also profoundly alters the susceptibility of cancer cells to T-cell-mediated immune surveillance. Furthermore, they reveal epithelial-to-mesenchymal transition and autophagy as conceptual realms for immunotherapeutic strategies to block immune escape.” ■

Akalay I, et al: Cancer Res 73:2418-2427, 2013.




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