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Review
. 2020 Sep 19:2020:9435030.
doi: 10.1155/2020/9435030. eCollection 2020.

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

Rodrigo Catalán  1   2 , Mario Orozco-Morales  2 , Norma Y Hernández-Pedro  2 , Alberto Guijosa  2 , Ana L Colín-González  2 , Federico Ávila-Moreno  3   4 , Oscar Arrieta  1   2
Affiliations
Review

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

Rodrigo Catalán et al. J Immunol Res. .

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.

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Conflict of interest statement

Dr. Arrieta reports personal fees from Pfizer, grants and personal fees from Astra Zeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Lilly, personal fees from Merck, personal fees from Bristol Myers Squibb, grants and personal fees from Roche, outside the submitted work. All the remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The CD47-SIRPα interaction plays a key role in phagocytosis inhibition. The CD47-SIRPα interaction leads to the phosphorylation of two tyrosine residues in the ITIM motif included in SIRPα's cytosolic domain. Phosphorylation recruits and activates SHP1 & SHP2, signaling a cascade of events that leads to the dephosphorylation of myosin IIA and, therefore, inhibition of the cytoskeleton rearrangement, which is a necessary step for macrophages to engulf target cells. In tumor cells, the enhanced activity of the CD47-SIRPα axis is achieved by increasing CD47 expression.
Figure 2
Figure 2
Promising treatment combinations of anti-CD47 drugs and current effective therapies for NSCLC. The inhibition of the CD47-SIRPα axis with anti-CD47 mAb can induce antitumor immunity through various mechanisms. Combining anti-CD47 with TKIs might be beneficial for two reasons. First, EGFR inhibition has shown to significantly reduce CD47 expression. Second, the inhibition of CD47 could increase the clearance of TKI-resistant cells. Combining anti-CD47 with antiangiogenic therapy could likewise be useful, since CD47 blockade could sensitize NSCLC to the latter therapy and potentiate its antitumor effects.
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