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Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer
Author(s) -
Russo Eleonora,
Santoni Angela,
Bernardini Giovanni
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.5mr0320-205r
Subject(s) - biology , immune system , chemokine , cancer research , cancer cell , myeloid derived suppressor cell , stromal cell , tumor microenvironment , cancer immunotherapy , immunology , cytotoxic t cell , cxcr3 , cancer , immunotherapy , chemokine receptor , suppressor , genetics , in vitro , biochemistry
Tumor tissue includes cancer cells and normal stromal cells such as vascular endothelial cells, connective tissue cells (cancer associated fibroblast, mesenchymal stem cell), and immune cells (tumor‐infiltrating lymphocytes or TIL, dendritic cells, eosinophils, basophils, mast cells, tumor‐associated macrophages or TAM, myeloid‐derived suppressor cells or MDSC). Anti‐tumor activity is mainly mediated by infiltration of NK cells, Th1 and CD8 + T cells, and correlates with expression of NK cell and T cell attracting chemokines. Nevertheless, cancer cells hijack tissue homeostasis through secretion of cytokines and chemokines that mediate not only the induction of an inflamed status that supports cancer cell survival and growth, but also the recruitment and/or activation of immune suppressive cells. CXCL9, CXCL10, and CXCL11 are known for their tumor‐inhibiting properties, but their overexpression in several hematologic and solid tumors correlates with disease severity, suggesting a role in tumor promotion. The dichotomous nature of CXCR3 ligands activity mainly depends on several molecular mechanisms induced by cancer cells themselves able to divert immune responses and to alter the whole local environment. A deep understanding of the nature of such phenomenon may provide a rationale to build up a CXCR3/ligand axis targeting strategy. In this review, we will discuss the role of CXCR3 in cancer progression and in regulation of anti‐tumor immune response and immunotherapy.