A T-cell antigen atlas for meningioma: novel options for immunotherapy.

in Acta neuropathologica by Gioele Medici, Lena K Freudenmann, Julia Velz, Sophie Shih-Yüng Wang, Konstantina Kapolou, Nagarajan Paramasivam, Lena Mühlenbruch, Daniel J Kowalewski, Flavio Vasella, Tatjana Bilich, Beat M Frey, Marissa L Dubbelaar, Angelica Brooke Patterson, Anna Maria Zeitlberger, Manuela Silginer, Patrick Roth, Tobias Weiss, Hans-Georg Wirsching, Niklaus Krayenbühl, Oliver Bozinov, Luca Regli, Hans-Georg Rammensee, Elisabeth Jane Rushing, Felix Sahm, Juliane S Walz, Michael Weller, Marian C Neidert

TLDR

  • The study is trying to find out what makes meningiomas different from other things in the body. They used a special machine to look at the proteins that are made by the cells in meningiomas and compared them to the proteins made by normal cells. They found some proteins that are only made by meningioma cells and these proteins could be used as targets for a special kind of treatment called immunotherapy. The study also looked at how well these proteins work as targets for immunotherapy by testing them on special cells called T-cells. The study's findings could help doctors find new ways to treat meningiomas.

Abstract

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Overview

  • The study aims to identify T-cell antigens in meningiomas using LC-MS/MS and compare them to normal tissues. The study identifies meningioma-exclusive antigens for HLA class I and II, which could be used as targets for immunotherapy. The study also functionally characterizes the identified antigens through in vitro T-cell priming assays. The study provides an atlas of meningioma T-cell antigens that will be publicly available for further research. The study's primary objective is to identify novel actionable targets for immunotherapy in meningiomas.

Comparative Analysis & Findings

  • The study compares the T-cell antigens identified in meningiomas to those in normal tissues. The study identifies meningioma-exclusive antigens for HLA class I and II, which could be used as targets for immunotherapy. The study also functionally characterizes the identified antigens through in vitro T-cell priming assays. The study's key findings are the identification of novel actionable targets for immunotherapy in meningiomas.

Implications and Future Directions

  • The study's findings have significant implications for the field of immunotherapy in meningiomas. The study identifies novel actionable targets for immunotherapy that could be used to treat meningiomas. The study's atlas of meningioma T-cell antigens will be publicly available for further research. The study's limitations include the small sample size and the need for further validation of the identified targets. Future research directions could include the development of immunotherapies targeting the identified meningioma-exclusive antigens and the validation of the identified targets in larger patient cohorts.
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