Glioblastoma, an opportunity T cell trafficking could bring for the treatment

Mol Biol Rep. 2022 Oct;49(10):9863-9875. doi: 10.1007/s11033-022-07510-1. Epub 2022 May 23.

Abstract

Purpose: Infiltrating into the vital structure of the brain, located in the inaccessible anatomical region, and having molecular heterogeneity, glioblastoma (GBM) -with no doubt- is one of the deadliest cancers. Using the blood and brain barrier (BBB), GBM makes a shield to restrict the reach of chemotherapeutic agents to the tumor site and evolves a unique microenvironment to furnish all the essentials for cancer cells survival to conceal neoplastic cells from immunosurveillance.

Methods: 99 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence.

Results: Given this characteristic, immunotherapies for a while enjoyed unprecedented attention as a solution for GBM treatment; however, it did not take long before the enthusiasm for their application was muted. It became apparent that cancer cells intelligently find a way to manipulate the anti-tumor responses of agents by attracting immunosuppressive lymphocytes into the brain using the lymphatic vessels. This event makes GBM a good model for immunotherapy resistance. However, the presence of lymphatic vessels has fired up an idea of the adoptive attraction of effector T lymphocytes to the tumor milieu. This was when engineering and cloning technologies, which have given life to one of the recent treatment strategies using artificial T cells named chimeric antigen receptors (CAR) T-cells, came to action to design specific CAR T-cells for the treatment of GBM.

Conclusion: The present review summarizes the recent advances in CAR T-cell-based treatments in GBM and discusses why this approach could be positioned as a pillar of the next-generation of immunotherapies for this type of brain tumor.

Keywords: CAR T-cells; Glioblastoma; Immunotherapy; T cell Trafficking.

Publication types

  • Review

MeSH terms

  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / therapy
  • Glioblastoma* / metabolism
  • Humans
  • Immunotherapy, Adoptive
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment

Substances

  • Receptors, Chimeric Antigen