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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1347404
This article is part of the Research Topic New Insights in Cytokines and Tumor Immunotherapy View all 4 articles

Cytokine screening identifies TNF to potentially enhance immunogenicity of pediatric sarcomas

Provisionally accepted
Hendrik Gaßmann Hendrik Gaßmann 1*Melanie Thiede Melanie Thiede 1Jennifer Eck Jennifer Eck 1Emilie Biele Emilie Biele 1Helena Lachermeier Helena Lachermeier 1Valentina Evdokimova Valentina Evdokimova 2Laszlo Radvanyi Laszlo Radvanyi 2Irfan Akhtar Irfan Akhtar 1Mina N. Morcos Mina N. Morcos 1Franziska Auer Franziska Auer 1Sebastian J. Schober Sebastian J. Schober 1Julia Hauer Julia Hauer 1Uwe Thiel Uwe Thiel 1Kristina Heyking Kristina Heyking 1*
  • 1 Technical University of Munich, Munich, Germany
  • 2 ontario institute for cancer research, Toronto, Canada

The final, formatted version of the article will be published soon.

    Pediatric sarcomas, including osteosarcoma (OS), Ewing sarcoma (EwS) and rhabdomyosarcoma (RMS) carry low somatic mutational burden and low expression of MHC-I expressionmolecules, posing a challenge for T cell therapies. Our previous study showed that mediators of monocyte maturation sensitized the EwS cell line A673 to lysis by HLA-A*02:01/CHM1 319 -specific allorestricted T cell receptor (TCR) transgenic CD8 + T cells (CHM1 319 CD8 + T cells). In this study, we tested a panel of monocyte maturation cytokines for their ability to upregulate immunogenic cell surface markers on OS, EwS and RMS cell lines. We observed that TNF and IL-1β upregulated MHC class I, ICAM-1 as well as CD83 and PD-L1 on the surface of pediatric sarcoma cell lines, while IL-4, GM-CSF, IL-6 and PGE2 failed to induce respective effects. Although pretreatment of pediatric sarcoma cell lines with TNF did not improve unspecific peripheral blood mononuclear cells (PBMCs) cytotoxicity, TNF enhanced specific recognition lysis of 1/3 HLA-A2 + EwS cell lines by CHM1 319 CD8 + T cells depending on MHC-I expression and ICAM-1 upregulation. Our study supports utilization of TNF or TNF-inducing regimens for upregulation of MHC-I and costimulatory surface molecules on pediatric sarcoma cells and for enhancing recognition of responsive HLA-A2-positive EwS tumor cells by antigen-specific CD8 + T cells.

    Keywords: Pediatric sarcomas, Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Immunotherapy, Adoptive T cell Transfer, MHC-I, TNF

    Received: 30 Nov 2023; Accepted: 04 Oct 2024.

    Copyright: © 2024 Gaßmann, Thiede, Eck, Biele, Lachermeier, Evdokimova, Radvanyi, Akhtar, Morcos, Auer, Schober, Hauer, Thiel and Heyking. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hendrik Gaßmann, Technical University of Munich, Munich, Germany
    Kristina Heyking, Technical University of Munich, Munich, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.