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

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.

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Fig. 1

Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Code availability

Not applicable.

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The first draft of the manuscript was written by [Mehdi Karimi-Shahri, Malihe Khorramdel, Sara Zarei, Fatemeh Attarian], and the figure and tables appropriate to the text of the manuscript were designed by Pedram Hashemian, and all authors commented on previous versions of the manuscript. Finally, all authors read and approved the final manuscript. Hossein Javid was responsible for coordinating the authors, finalized, and submitting the paper.

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Correspondence to Hossein Javid.

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Mehdi Karimi-Shahri and Malihe Khorramdel co-first authors.

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Karimi-Shahri, M., Khorramdel, M., Zarei, S. et al. Glioblastoma, an opportunity T cell trafficking could bring for the treatment. Mol Biol Rep 49, 9863–9875 (2022). https://doi.org/10.1007/s11033-022-07510-1

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Keywords

  • Glioblastoma
  • T cell Trafficking
  • CAR T-cells
  • Immunotherapy