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Epithelial Mesenchymal Transition Influence on CTL Activity

  • Chapter
Resistance of Cancer Cells to CTL-Mediated Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 7))

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Abstract

Epithelial-mesenchymal transition (EMT) is a fundamental process orchestrating embryonic morphogenesis that also operates during carcinoma progression to promote invasion and metastasis. This review critically assesses whether EMT confers stemness, resistance to chemo- and targeted therapeutics, and immune escape. EMT inducers share common targets that alter apico-basal polarity, intercellular adhesion and the actin cytoskeleton, events that also contribute to the transdifferentiation of epithelial into mesenchymal cells. The considerable genomic heterogeneity exhibited by tumors, concomitant with their rapidly evolving sub-clones, is a major caveat in the success of targeted therapeutics. With the recent spectacular progress in immunotherapy for some solid tumors, one can now envision expanding upon this strategy for other tumors, pending the improved efficacy of T lymphocyte-mediated cytotoxicity. This review explores how the immunological synapse can be affected by EMT and posits how EMT reversal by kinase inhibitors could help restore a functional immunological synapse, in cooperation with antibodies abrogating immune suppression.

No potential conflicts of interest were disclosed.

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Abbreviations

ALDH1:

Aldehyde dehydrogenase-1

APC:

Antigen presenting cell

CK1:

Casein kinase 1

cSMAC:

Central supra-molecular activation cluster

CT:

Computed tomography

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T lymphocyte associated protein 4

dSMAC:

Distal supramolecular activation cluster

EGF:

Epidermal growth factors

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal Transition

ERBB2:

Receptor tyrosine-protein kinase

FGF:

Fibroblast growth factor

GSK3b:

Glycogen synthase 1

HGF:

Hepatocyte growth factor

HMLE:

Human mammary epithelial cell line

h-TERT:

Human telomerase reverse transcriptase

ICAM-1:

Intercellular adhesion molecule-1

IGF:

Insulin-like growth factor

LFA-1:

Lymphocyte function associated antigen-1

MAPK:

Mitogen activated protein kinase

MCF7:

Epithelial mammary adenocarcinoma cell line

MHC:

Major histocompatibility antigen

miRNA:

MicroRNAs

MRI:

Magnetic resonance imaging

NSCLC:

Non-small cell lung cancer

PD-1:

Programmed death-1 protein

PD-1 L:

Programmed death-1 protein ligand

PET:

Positron emission tomography

PI3K:

phosphoinositide 3-kinase

pMHCs:

Peptide-bound major histocompatibility complex

PRC:

Polycomb repressor complex

pSMAC:

Peripheral supra-molecular activation cluster

SHP2:

Tyrosine-protein phosphatase non-receptor type 11

TCR:

T-cell surface receptors

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

Treg :

Regulatory T cell

WISP2:

Wnt1-inducible signaling pathway protein 2

ZAP70:

Zeta-chain-associated protein kinase 70

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Acknowledgements

The authors would like to thank Rebecca Anne Jackson for her excellent editing. JP Thiery is supported by core grants from IMCB and NUS.

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Authors and Affiliations

  1. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

    Wilfried Engl & Virgile Viasnoff

  2. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD7, 8 Medical Drive, Singapore, 117597, Singapore

    Jean Paul Thiery

  3. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Jean Paul Thiery

  4. Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore

    Jean Paul Thiery

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  1. Wilfried Engl
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  2. Virgile Viasnoff
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Correspondence to Jean Paul Thiery .

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Editors and Affiliations

  1. Department of Microbiology, Immunology a, University of California at Los Angeles,, Los Angeles, California, USA

    Benjamin Bonavida

  2. Institut Gustave Roussy, Villejuif, France

    Salem Chouaib

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Engl, W., Viasnoff, V., Thiery, J.P. (2015). Epithelial Mesenchymal Transition Influence on CTL Activity. In: Bonavida, B., Chouaib, S. (eds) Resistance of Cancer Cells to CTL-Mediated Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-17807-3_12

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