The mutually regulatory loop of epithelial–mesenchymal transition and immunosuppression in cancer progression

Abstract

Epithelial-mesenchymal transition and immunosuppression are crucial for cancer metastasis and treatment resistance. The mechanism by which these distinct processes are co-opted remains incompletely understood. Our recent work has exposed the "dirty affairs" of the 2 at the tumor site, thus calling for a combined therapy to break such a dangerous liaison.

Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression

“…It is well accepted that EMT has a critical impact on immunosuppression during tumor progression. 13,14,43,51 Consistent with this notion, BMP4, as a downstream mediator of EMT, forges a strong immunosuppressive microenvironment upon loss of miR-200 expression in tumors.…”

“…3,13,14,42,43 EMT is a critically important pathway during embryogenesis that is frequently reactivated during tumor progression. An increasing number of studies have examined the EMT state and intratumoral factors that lead to the development of an immunosuppressive tumor microenvironment, 13,43,44 suggesting that multiple parallel pathways are activated that may suppress an effective antitumor immune response.…”

“…[1][2][3][4][5] The types of inflammatory cells that infiltrate tumors correlate with patient prognosis. [6][7][8][9] Although tumor cells control the abundance and function of tumor-infiltrating immune cells to create a milieu that supports tumor growth and dissemination, [10][11][12][13][14] the specific genes expressed in tumor cells that create an immunosuppressive microenvironment have not been fully defined.…”

Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma

“…Co-enrichment of these signatures, collectively referred to as the Innate anti-PD-1 Resistance or IPRES signature, again indicated heightened mesenchymal transition, angiogenesis, hypoxia and wound healing. The concurrence of a tumor cell mesenchymal phenotype with an angiogenesis-and wound healing-related inflammatory microenvironment has been documented in the literature (Chen et al, 2015a;Chen et al, 2015b;Mak et al, 2015). Interestingly, this set of 26 IPRES signatures included signatures induced by MAPK inhibitor (MAPKi) treatment of melanoma tumors and cell lines (Table S2C).…”

A Blueprint to Advance Colorectal Cancer Immunotherapies

“…A signature consisting of an angiogenic and wound healingrelated microenvironment has been documented (20)(21)(22). Understanding the immune context and the TME will play a vital role in designing strategies to improve immune function.…”