Tumoral and paratumoral NK cells and CD8+ T cells of esophageal carcinoma patients express high levels of CD47

Zuzana Strizova,Jiri Vachtenheim,Martin Snajdauf,Robert Lischke,Daniel Smrz,Jirina Bartunkova

doi:10.1038/s41598-020-70771-y

Zuzana Strizova, Jiri Vachtenheim + Show 4 more

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https://doi.org/10.1038/s41598-020-70771-y

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Journal: Scientific Reports	Publication Date: Aug 18, 2020
Citations: 12	License type: open-access

Affiliation: Charles University

Abstract

In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. However, the CD47 expression pattern in tumor-infiltrating lymphocytes (TILs), which are associated with prolonged overall survival and serve as a positive prognostic factor, is largely unknown. In this study, a total of 36 tissue samples from the tumor, peritumoral tissue, and adjacent healthy esophageal tissue was obtained from 12 esophageal carcinoma (EC) patients, and the surface expression of CD47 was evaluated in natural killer (NK) cells, CD8+ T cells, and the nonlymphocyte cell fraction. We found that the proportions of the evaluated cells and their CD47-expressing populations were comparable across the analyzed tissue compartments. However, the proportions of CD47-expressing populations in the analyzed tissue compartments were significantly higher in NK cells and CD8+ T cells than in the nonlymphocyte cell fraction. Importantly, the intensity of CD47 staining was also significantly higher in the tested immune cells than in the nonlymphocyte cell fraction. High expression of CD47 in tissue-infiltrating NK cells and CD8+ T cells in EC patients can, therefore, affect the efficacy of anti-CD47 therapy in EC.

Highlights

In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages
No significant differences were found in the proportions of natural killer (NK) cells ( CD45+CD3−CD56+ cells), T cells (CD45+CD3+CD8+ cells), or the nonlymphocyte population ( CD45− cells) among the analyzed tissue compartments (Fig. 1B). These data showed that compared with paratumoral tissues, the analyzed tumors were not infiltrated with more NK cells or CD8+ T cells
We show that in addition to tumor cells, the majority of tumoral and paratumoral NK cells and CD8+ T cells express CD47, and the levels of its expression are even higher than in the parallel nonlymphocyte cells

Summary

Introduction

In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. High expression of CD47 in tissue-infiltrating NK cells and C D8+ T cells in EC patients can, affect the efficacy of anti-CD47 therapy in EC. In vitro experiments have shown that blocking CD47‐SIRPα signaling with anti‐CD47 antibodies increases the phagocytosis of CD47-expressing ESCC tumor cells by macrophages in a dose-dependent m anner[13]. These findings indicate that anti-CD47 therapy could be an effective treatment modality for ESCC13.

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