1. CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma
- Author
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Marco Bianchi, Francesca Sanvito, Rosanna Mezzapelle, Ottavio Rena, Lina Sabatino, Vittorio Colantuoni, Francesca Caprioglio, Federica Colombo, Patrizia Castellani, Maura Casalgrandi, Francesca Brambilla, Chiara Passera, Manuela Leo, Angelo Carretta, Veronica Basso, Anna Rubartelli, Francesco De Marchis, Massimo P. Crippa, Samuel Zambrano, Renzo Boldorini, Marco Silingardi, Anna Mondino, Alessandro Preti, Riccardo Ertassi, Mezzapelle, R., De Marchis, F., Passera, C., Leo, M., Brambilla, F., Colombo, F., Casalgrandi, M., Preti, A., Zambrano, S., Castellani, P., Ertassi, R., Silingardi, M., Caprioglio, F., Basso, V., Boldorini, R., Carretta, A., Sanvito, F., Rena, O., Rubartelli, A., Sabatino, L., Mondino, A., Crippa, M. P., Colantuoni, V., and Bianchi, M. E.
- Subjects
0301 basic medicine ,Mesothelioma ,Medicine (General) ,media_common.quotation_subject ,Immunology ,Priming (immunology) ,CD47 Antigen ,QH426-470 ,Article ,03 medical and health sciences ,Mice ,R5-920 ,0302 clinical medicine ,Phagocytosis ,Cell Line, Tumor ,immunogenic cell death ,Genetics ,Cytotoxic T cell ,Medicine ,Animals ,Internalization ,CD47 ,media_common ,Cancer ,CXCR4 ,HMGB1 ,biology ,business.industry ,Macrophages ,Articles ,Tumor antigen ,030104 developmental biology ,Tumor progression ,mesothelioma ,Cancer research ,biology.protein ,Molecular Medicine ,Immunogenic cell death ,Immunization ,Antibody ,business ,030217 neurology & neurosurgery - Abstract
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., Induction of antitumor immunity is a successful strategy in cancer treatment. This study reports that BoxA, a fragment of the alarmin HMGB1, induces tumor remission and antitumor immunity in mouse models of mesothelioma and colon carcinoma.
- Published
- 2021