The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies

Front Immunol. 2023 Jun 16:14:1154146. doi: 10.3389/fimmu.2023.1154146. eCollection 2023.

Abstract

Glioblastoma is the most common primary malignant tumor of the central nervous system, which has the characteristics of strong invasion, frequent recurrence, and rapid progression. These characteristics are inseparable from the evasion of glioma cells from immune killing, which makes immune escape a great obstacle to the treatment of glioma, and studies have confirmed that glioma patients with immune escape tend to have poor prognosis. The lysosomal peptidase lysosome family plays an important role in the immune escape process of glioma, which mainly includes aspartic acid cathepsin, serine cathepsin, asparagine endopeptidases, and cysteine cathepsins. Among them, the cysteine cathepsin family plays a prominent role in the immune escape of glioma. Numerous studies have confirmed that glioma immune escape mediated by lysosomal peptidases has something to do with autophagy, cell signaling pathways, immune cells, cytokines, and other mechanisms, especially lysosome organization. The relationship between protease and autophagy is more complicated, and the current research is neither complete nor in-depth. Therefore, this article reviews how lysosomal peptidases mediate the immune escape of glioma through the above mechanisms and explores the possibility of lysosomal peptidases as a target of glioma immunotherapy.

Keywords: autophagy; cathepsin; cell signal pathways; glioma; immune escape; lysosomal peptidases.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsins / metabolism
  • Cysteine
  • Glioma* / pathology
  • Glioma* / therapy
  • Humans
  • Lysosomes / metabolism
  • Peptide Hydrolases*

Substances

  • Peptide Hydrolases
  • Cysteine
  • Cathepsins

Grants and funding

The research project is supported by the National Natural Science Foundation (grant nos. 81860448, 82002660 and 82172989), the Natural Science Foundation of Jiangxi Province (grant no.20192BAB205077 and 20202ACB216004), the Jiangxi Key research and development projects-Key Project (20212BBG71012), Jiangxi Provincial Science and Technology Innovation Base Plan-Provincial Key Laboratory (20212BCD42008), Construction of Science and Technology Innovation Base-Clinical Medicine Research Center (2021ZDG02001), Jiangxi Key research and development projects (20212BBG73021), Province-Youth Talent Project (20212BCJ23023).