CD47-SIRP α Axis as a Biomarker and Therapeutic Target in Cancer: Current Perspectives and Future Challenges in Nonsmall Cell Lung Cancer

J Immunol Res. 2020 Sep 19:2020:9435030. doi: 10.1155/2020/9435030. eCollection 2020.

Abstract

CD47 is a cell surface protein in the immunoglobulin superfamily which is normally expressed at low levels in every healthy cell. It´s main physiologic function is to act as an inhibitor of phagocytosis; this occurs throughout interaction with SIRPa expressed on macrophages. Interaction between CD47 and SIRPa leads to activation of tyrosine phosphatases that inhibit myosin accumulation at the submembrane assembly site of the phagocytic synapse, resulting in phagocytosis blockade. In this way CD47 acts as a "don´t eat me signal" for healthy self-cells; accordingly, loss of CD47 leads to phagocytosis of aged or damaged cells. Taking advantage of this anti-phagocytic signal provided by CD47, many types of tumors overexpress this protein, thereby avoiding phagocytosis by macrophages and aiding in the survival of cancer cells. The aim of this review is to describe the physiologic the pathophysiologic role of CD47; summarize the available high-quality information about this molecule as a potential biomarker and/or therapeutic target in cancer; finally, we present an in-depth analysis of the available information about CD47 in association with nonsmall cell lung cancer, EGFR mutations, and tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Antigens, Differentiation / metabolism*
  • Biomarkers, Tumor*
  • CD47 Antigen / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Management
  • Disease Susceptibility
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / etiology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Prognosis
  • Receptors, Immunologic / metabolism*
  • Treatment Outcome

Substances

  • Antigens, Differentiation
  • Biomarkers, Tumor
  • CD47 Antigen
  • CD47 protein, human
  • Receptors, Immunologic
  • SIRPA protein, human