Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer

Tumor cells undergoing epithelial to mesenchymal transition (EMT) and immune cells in tumor microenvironment (TME) reciprocally influence each other. Immune cells, by supplying TME with bioactive molecules including cytokines, chemokines, enzymes, metabolites, and by physical interactions with tumor...

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Auteurs principaux:	Ana Vuletić, Katarina Mirjačić Martinović, Nevena Tišma Miletić, Jerome Zoidakis, Sergi Castellvi-Bel, Milena Čavić
Format:	article
Langue:	EN
Publié:	Frontiers Media S.A. 2021
Sujets:	NK cells tumor microenvironment NK cell receptors epithelial to mesenchymal transition colorectal cancer Biology (General) QH301-705.5
Accès en ligne:	https://doaj.org/article/a696b5ce38d34ab3ab755608e089a16f
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spelling	oai:doaj.org-article:a696b5ce38d34ab3ab755608e089a16f2021-11-10T07:44:20ZCross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer2296-634X10.3389/fcell.2021.750022https://doaj.org/article/a696b5ce38d34ab3ab755608e089a16f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.750022/fullhttps://doaj.org/toc/2296-634XTumor cells undergoing epithelial to mesenchymal transition (EMT) and immune cells in tumor microenvironment (TME) reciprocally influence each other. Immune cells, by supplying TME with bioactive molecules including cytokines, chemokines, enzymes, metabolites, and by physical interactions with tumor cells via their receptors, represent an important factor that affects EMT. Chronical inflammation in TME favorizes tumor growth and invasiveness and stimulates synthesis of EMT promoting transcription factors. Natural killer (NK) cells, owing to their unique ability to exert cytotoxic function independent of major histocompatibility (MHC)-mediated antigen presentation, play a significant role in the control of metastasis in colorectal cancer (CRC). Although, the cross-talk between immune cells and tumor cells in general favors the induction of EMT and inhibition of antitumor immune responses, there are some changes in the immunogenicity of tumor cells during EMT of CRC cells that increase their susceptibility to NK cell cytotoxic lysis. However, suppressive TME downmodulates the expression of activating NK cell receptors, decreases the expression of activating and increases the expression of inhibitory NK cell ligands on tumor cells, and impairs NK cell metabolism that altogether negatively affects the overall NK cell function. Furthermore, process of EMT is often associated with increased expression of programmed cell death ligand (PD-L) and expression of immune checkpoint molecules PD-1, TIGIT, and TIM3 on functionally exhausted NK cells in TME in CRC. In this review we discuss modalities of cross-talk between tumor cells and NK cells, with regard of EMT-driven changes.Ana VuletićKatarina Mirjačić MartinovićNevena Tišma MiletićJerome ZoidakisSergi Castellvi-BelMilena ČavićFrontiers Media S.A.articleNK cellstumor microenvironmentNK cell receptorsepithelial to mesenchymal transitioncolorectal cancerBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NK cells tumor microenvironment NK cell receptors epithelial to mesenchymal transition colorectal cancer Biology (General) QH301-705.5
spellingShingle	NK cells tumor microenvironment NK cell receptors epithelial to mesenchymal transition colorectal cancer Biology (General) QH301-705.5 Ana Vuletić Katarina Mirjačić Martinović Nevena Tišma Miletić Jerome Zoidakis Sergi Castellvi-Bel Milena Čavić Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
description	Tumor cells undergoing epithelial to mesenchymal transition (EMT) and immune cells in tumor microenvironment (TME) reciprocally influence each other. Immune cells, by supplying TME with bioactive molecules including cytokines, chemokines, enzymes, metabolites, and by physical interactions with tumor cells via their receptors, represent an important factor that affects EMT. Chronical inflammation in TME favorizes tumor growth and invasiveness and stimulates synthesis of EMT promoting transcription factors. Natural killer (NK) cells, owing to their unique ability to exert cytotoxic function independent of major histocompatibility (MHC)-mediated antigen presentation, play a significant role in the control of metastasis in colorectal cancer (CRC). Although, the cross-talk between immune cells and tumor cells in general favors the induction of EMT and inhibition of antitumor immune responses, there are some changes in the immunogenicity of tumor cells during EMT of CRC cells that increase their susceptibility to NK cell cytotoxic lysis. However, suppressive TME downmodulates the expression of activating NK cell receptors, decreases the expression of activating and increases the expression of inhibitory NK cell ligands on tumor cells, and impairs NK cell metabolism that altogether negatively affects the overall NK cell function. Furthermore, process of EMT is often associated with increased expression of programmed cell death ligand (PD-L) and expression of immune checkpoint molecules PD-1, TIGIT, and TIM3 on functionally exhausted NK cells in TME in CRC. In this review we discuss modalities of cross-talk between tumor cells and NK cells, with regard of EMT-driven changes.
format	article
author	Ana Vuletić Katarina Mirjačić Martinović Nevena Tišma Miletić Jerome Zoidakis Sergi Castellvi-Bel Milena Čavić
author_facet	Ana Vuletić Katarina Mirjačić Martinović Nevena Tišma Miletić Jerome Zoidakis Sergi Castellvi-Bel Milena Čavić
author_sort	Ana Vuletić
title	Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
title_short	Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
title_full	Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
title_fullStr	Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
title_full_unstemmed	Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer
title_sort	cross-talk between tumor cells undergoing epithelial to mesenchymal transition and natural killer cells in tumor microenvironment in colorectal cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a696b5ce38d34ab3ab755608e089a16f
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Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer

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