CXCR4/CXCL12 Activities in the Tumor Microenvironment and Implications for Tumor Immunotherapy
Rosanna Mezzapelle, M. Di Leo, Francesca Caprioglio, Liam Colley, Andrea Lamarca, Lina Sabatino, Vittorio Colantuoni, Massimo P. Crippa, Marco E. Bianchi
Abstract
CXCR4 is a G-Protein coupled receptor that is expressed nearly ubiquitously and is known to control cell migration via its interaction with CXCL12, the most ancient chemokine. The functions of CXCR4/CXCL12 extend beyond cell migration and involve the recognition and disposal of unhealthy or tumor cells. The CXCR4/CXCL12 axis plays a relevant role in shaping the tumor microenvironment (TME), mainly towards dampening immune responses. Notably, CXCR4/CXCL12 cross-signal via the T and B cell receptors (TCR and BCR) and co-internalize with CD47, promoting tumor cell phagocytosis by macrophages in an anti-tumor immune process called ImmunoGenic Surrender (IGS). These specific activities in shaping the immune response might be exploited to improve current immunotherapies.