Open AccessCXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma
Author(s) -
Mezzapelle Rosanna,
De Marchis Francesco,
Passera Chiara,
Leo Manuela,
Brambilla Francesca,
Colombo Federica,
Casalgrandi Maura,
Preti Alessandro,
Zambrano Samuel,
Castellani Patrizia,
Ertassi Riccardo,
Silingardi Marco,
Caprioglio Francesca,
Basso Veronica,
Boldorini Renzo,
Carretta Angelo,
Sanvito Francesca,
Rena Ottavio,
Rubartelli Anna,
Sabatino Lina,
Mondino Anna,
Crippa Massimo P,
Colantuoni Vittorio,
Bianchi Marco E
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202012344
Subject(s) - chromatin , library science , biology , genetics , computer science , dna
Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T‐cell brakes has received most attention, tumor recognition by T cells is a pre‐requisite. Radiotherapy and certain cytotoxic drugs induce the release of damage‐associated molecular patterns, which promote tumor antigen cross‐presentation and T‐cell priming. Antibodies against the “do not eat me” signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors.