The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Md Rakibul Alam; Md Mizanur Rahman; Zhiguo Li

doi:10.1016/j.gendis.2023.01.026

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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Review Articles | 更新时间：2024-02-04

- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy
- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy
- Genes & Diseases 2024年1卷第1期页码：321-334
- 作者机构：
  
  1. Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky,KY,Lexington,USA,40506
  2. Department of Medicine (Nephrology), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6E2H7,Canada
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.01.026
  中图分类号：
- 纸质出版日期：2024，
  
  网络出版日期：2024-1-1，
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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy[J]. Genes & Diseases, 2024,1(1):321-334.

Md Rakibul Alam, Md Mizanur Rahman, Zhiguo Li. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy[J]. Genes & Diseases, 2024,1(1):321-334.
The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy[J]. Genes & Diseases, 2024,1(1):321-334. DOI： 10.1016/j.gendis.2023.01.026.

Md Rakibul Alam, Md Mizanur Rahman, Zhiguo Li. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy[J]. Genes & Diseases, 2024,1(1):321-334. DOI： 10.1016/j.gendis.2023.01.026.

摘要

Abstract

Exosomes are small membrane vesicles containing microRNA

RNA

DNA fragments

and proteins that are transferred from donor cells to recipient cells. Tumor cells release exosomes to reprogram the factors associated with the tumor microenvironment (TME) causing tumor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with receptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently

some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes

some patients show poor drug response. Exosomal PD-L1 plays a vital role in lowering the treatment response

showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the effect of cell surface PD-L1. To enhance therapeutic response

inhibition of exosomal PD-L1 is required. Calcium signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion factors. Immune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine

nifedipine

lercanidipine

diltiazem

and verapamil were also reported to suppress cellular PD-L1 expression. Therefore

to enhance the PD-1/PD-L1 blockage therapy response

the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic consideration. In this review

we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词

Keywords

Calcium signalingCD8+T cellsExosomal PD-L1Exosomes biogenesisImmunosuppressionImmunotherapy

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