@article{bf597d58fe8440c0bcc96fea1dc08de1,
title = "Targeting the interplay between epithelial-to-mesenchymal-transition and the immune system for effective immunotherapy",
abstract = "Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo-and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We discuss why, despite breakthrough progress in immunotherapy, attaining predictable outcomes in the clinic is mostly an unsolved problem for these tumors. Although these two cancer types appear different based upon their tissues of origin and molecular classification, gene expression indicate that they possess many similarities. Patient tumors exhibit activation of EMT, and resulting stem cell properties in both these cancer types associate with metastasis and resistance to existing cancer therapies. In addition, the EMT transition in both these cancers plays a crucial role in immunosuppression, which exacerbates treatment resistance. To improve cancer-related survival we need to understand and circumvent, the mechanisms through which these tumors become therapy resistant. In this review, we discuss new information and complementary perspectives to inform combination treatment strategies to expand and improve the anti-tumor responses of currently available clinical immune checkpoint inhibitors.",
keywords = "CD8 T Cells, Immune blockade, NSCLC, Reversal of EMT, TNBC, Tumor microenvironment, Tumor plasticity",
author = "Rama Soundararajan and Fradette, {Jared J.} and Konen, {Jessica M.} and Stacy Moulder and Xiang Zhang and Gibbons, {Don L.} and Navin Varadarajan and Wistuba, {Ignacio I.} and Debasish Tripathy and Chantale Bernatchez and Byers, {Lauren A.} and Chang, {Jeffrey T.} and Alejandro Contreras and Bora Lim and Parra, {Edwin Roger} and Roarty, {Emily B.} and Jing Wang and Fei Yang and Michelle Barton and Rosen, {Jeffrey M.} and Mani, {Sendurai A.}",
note = "Funding Information: We thank NIH/NCI CCSG P30-CA01667 (L.A.B.), NIH/NCI SPORE P5-CA070907 (L.A.B.), an MD Andersen Cancer Center Physician Scientist Award (L.A.B.), LUNGevity Foundation (L.A.B.), philanthropic contributions to The University of Texas MD Anderson Cancer Center Lung Cancer Moonshot Program (L.A.B.), NIH R37 CA214609-01A1 (D.L.G.), CPRIT-MIRA-RP160652-P3 (D.L.G.), Rexanna{\textquoteright}s Foundation for Fighting Lung Cancer (D.L.G.), P50 CA070907 from UT Lung SPORE Career Enhancement Award (J.M.K.), NIH/NCI-R01CA200970 (S.A.M.), NIH/NCI-2R01CA155243 (S.A.M.), National Science Foundation-15-597-1605817 (S.A.M.), CPRIT-MIRA-RP160710 (S.A.M., Project-3), CPRIT-IIRA-RP170172 (J.M.R., S.A.M.), Diana Helis Henry and Andrienne Helis Malvin Medical Research Foundation Grant (J.M.R., X.Z.), P50 CA140388 from the National Cancer Institute (University of Texas MD Anderson Prostate Cancer SPORE Career Enhancement Program Award) (R.S.), MD Anderson Institutional Research Grant (R.S.), CPRIT-MIRA-RP180712 (D.T., Core), CPRIT-RP180466 (N.V.), MRA-509800 (N.V.), for financial support. Funding Information: Acknowledgments: We thank NIH/NCI CCSG P30-CA01667 (L.A.B.), NIH/NCI SPORE P5-CA070907 (L.A.B.), an MD Andersen Cancer Center Physician Scientist Award (L.A.B.), LUNGevity Foundation (L.A.B.), philanthropic contributions to The University of Texas MD Anderson Cancer Center Lung Cancer Moonshot Program (L.A.B.), NIH R37 CA214609-01A1 (D.L.G.), CPRIT-MIRA-RP160652-P3 (D.L.G.), Rexanna{\textquoteright}s Foundation for Fighting Lung Cancer (D.L.G.), P50 CA070907 from UT Lung SPORE Career Enhancement Award (J.M.K.), NIH/NCI-R01CA200970 (S.A.M.), NIH/NCI-2R01CA155243 (S.A.M.), National Science Foundation-15-597-1605817 (S.A.M.), CPRIT-MIRA-RP160710 (S.A.M., Project-3), CPRIT-IIRA-RP170172 (J.M.R., S.A.M.), Diana Helis Henry and Andrienne Helis Malvin Medical Research Foundation Grant (J.M.R., X.Z.), P50 CA140388 from the National Cancer Institute (University of Texas MD Anderson Prostate Cancer SPORE Career Enhancement Program Award) (R.S.), MD Anderson Institutional Research Grant (R.S.), CPRIT-MIRA-RP180712 (D.T., Core), CPRIT-RP180466 (N.V.), MRA-509800 (N.V.), for financial support. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = may,
doi = "10.3390/cancers11050714",
language = "English (US)",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}