Cell Reports
Volume 31, Issue 2, 14 April 2020, 107494
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Report
Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection

https://doi.org/10.1016/j.celrep.2020.03.058Get rights and content
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Highlights

  • CD47 “don’t-eat-me” signals are upregulated on infected cells

  • Antibody-mediated blockade of CD47 enhances APC function in vivo

  • Therapeutic CD47 blockade enhances T cell responses and speeds LCMV clearance

  • CD47 blockade works in a pathogen non-specific manner to enhance immunity

Summary

Paradoxically, early host responses to infection include the upregulation of the antiphagocytic molecule, CD47. This suggests that CD47 blockade could enhance antigen presentation and subsequent immune responses. Indeed, mice treated with anti-CD47 monoclonal antibody following lymphocytic choriomeningitis virus infections show increased activation of both macrophages and dendritic cells (DCs), enhancement of the kinetics and potency of CD8+ T cell responses, and significantly improved virus control. Treatment efficacy is critically dependent on both APCs and CD8+ T cells. In preliminary results from one of two cohorts of humanized mice infected with HIV-1 for 6 weeks, CD47 blockade reduces plasma p24 levels and restores CD4+ T cell counts. The results indicate that CD47 blockade not only enhances the function of innate immune cells but also links to adaptive immune responses through improved APC function. As such, immunotherapy by CD47 blockade may have broad applicability to treat a wide range of infectious diseases.

Keywords

CD47
LCMV
HIV-1
dendritic cells
innate immunity
adaptive immunity
checkpoint inhibitors

Cited by (0)

6

Present address: HIV Frontiers/Global Health Innovative Technology Solutions, Bill & Melinda Gates Foundation, Seattle, WA 98109, USA

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Lead Contact