The mechanism of low-dose radiation-induced upregulation of immune checkpoint molecule expression in lung cancer cells.

Abstract

INTRODUCTION:

This study explored the effect of low-dose radiation on the expression of immune checkpoint molecules in lung cancer cells and its mechanism, as well as the antitumour effect of combined low-dose radiation and immune checkpoint inhibitors.

METHODS:

Western blot analysis was used to assess the expression of the immune checkpoint molecules CD47, PD-L1, FGL-1 and CD155 in lung cancer cells after radiation. Western blotting was also used to explore changes in the JAK2/STAT3 pathway. CD8+ T lymphocyte infiltration in tumour tissues were assessed by immunohistochemistry in a mouse model. The inhibitory effect of low-dose radiation combined with PD-L1 or CD47 inhibitors on tumor growth was evaluated by measuring tumor volume.

RESULTS:

In response to low-dose irradiation, the expression of CD47 and PD-L1 in A549 and LLC cells was increased, the expression of p-JAK2 and p-STAT3 was also increased. AG490-mediated inhibition of the JAK2/STAT3 pathway before irradiation significantly reduced the expression of p-JAK2 and p-STAT3 in lung cancer cells, in the meantime, expression of CD47 and PD-L1 was also reduced. Conventional dose exposure exhibited the same trend. PD-L1 and CD47 protein levels increased after low-dose irradiation in an LLC tumour-bearing mouse model. Low-dose irradiation combined with PD-L1 or CD47 inhibitor treatment reduced levels of PD-L1 or CD47 in tumour tissues, increased the proportion of CD8+ T lymphocytes, and significantly inhibited tumour growth.

CONCLUSIONS:

Both low-dose and regular-dose irradiation upregulate expression of the immune checkpoint molecules CD47 and PD-L1 in lung cancer cells, and the mechanism may be related to the JAK2/STAT3 pathway. Furthermore, low-dose irradiation combined with PD-L1 or CD47 inhibitors significantly inhibits tumour growth.

• Authors: Xinan Wan, Mingxing Fang, Tingting Chen, Huihui Wang, Qin Zhou, Yongming Wei, Lin Zheng, Yu Zhou, Kai Chen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 608 Pg. 102-107 (06 11 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35397421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• B7-H1 Antigen
• CD47 Antigen
• Immune Checkpoint Proteins

Topics

• Animals
• B7-H1 Antigen (metabolism)
• CD47 Antigen
• Immune Checkpoint Proteins
• Lung Neoplasms (metabolism)
• Mice
• Up-Regulation