Tumor resistance mechanisms and their consequences on γδ T cell activation

Daniela Wesch; Dieter Kabelitz; Hans‐Heinrich Oberg

doi:10.1111/imr.12925

journal article Open Access Oct 13, 2020

Tumor resistance mechanisms and their consequences on γδ T cell activation

Daniela Wesch

Dieter Kabelitz

Hans‐Heinrich Oberg

Immunological Reviews Vol. 298 No. 1 pp. 84-98 · Wiley

View at Publisher Save 10.1111/imr.12925

Abstract

AbstractHuman γδ T lymphocytes are predominated by two major subsets, defined by the variable domain of the δ chain. Both, Vδ1 and Vδ2 T cells infiltrate in tumors and have been implicated in cancer immunosurveillance. Since the localization and distribution of tumor‐infiltrating γδ T cell subsets and their impact on survival of cancer patients are not completely defined, this review summarizes the current knowledge about this issue. Different intrinsic tumor resistance mechanisms and immunosuppressive molecules of immune cells in the tumor microenvironment have been reported to negatively influence functional properties of γδ T cell subsets. Here, we focus on selected tumor resistance mechanisms including overexpression of cyclooxygenase (COX)‐2 and indolamine‐2,3‐dioxygenase (IDO)‐1/2, regulation by tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/TRAIL‐R4 pathway and the release of galectins. These inhibitory mechanisms play important roles in the cross‐talk of γδ T cell subsets and tumor cells, thereby influencing cytotoxicity or proliferation of γδ T cells and limiting a successful γδ T cell‐based immunotherapy. Possible future directions of a combined therapy of adoptively transferred γδ T cells together with γδ‐targeting bispecific T cell engagers and COX‐2 or IDO‐1/2 inhibitors or targeting sialoglycan‐Siglec pathways will be discussed and considered as attractive therapeutic options to overcome the immunosuppressive tumor microenvironment.

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Details

Published: Oct 13, 2020
Vol/Issue: 298(1)
Pages: 84-98
License: View

Authors

D

Daniela Wesch

Institute of Immunology University Hospital Schleswig‐Holstein Christian‐Albrechts University of Kiel Kiel Germany

D

Dieter Kabelitz

Institute of Immunology University Hospital Schleswig‐Holstein Christian‐Albrechts University of Kiel Kiel Germany

H

Hans‐Heinrich Oberg

Institute of Immunology University Hospital Schleswig‐Holstein Christian‐Albrechts University of Kiel Kiel Germany

Cite This Article

Daniela Wesch, Dieter Kabelitz, Hans‐Heinrich Oberg (2020). Tumor resistance mechanisms and their consequences on γδ T cell activation. Immunological Reviews, 298(1), 84-98. https://doi.org/10.1111/imr.12925

Tumor resistance mechanisms and their consequences on γδ T cell activation

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