Activated B-Cells enhance epitope spreading to support successful cancer immunotherapy

Front Immunol. 2024 Mar 19:15:1382236. doi: 10.3389/fimmu.2024.1382236. eCollection 2024.

Abstract

Immune checkpoint therapies (ICT) have transformed the treatment of cancer over the past decade. However, many patients do not respond or suffer relapses. Successful immunotherapy requires epitope spreading, but the slow or inefficient induction of functional antitumoral immunity delays the benefit to patients or causes resistances. Therefore, understanding the key mechanisms that support epitope spreading is essential to improve immunotherapy. In this review, we highlight the major role played by B-cells in breaking immune tolerance by epitope spreading. Activated B-cells are key Antigen-Presenting Cells (APC) that diversify the T-cell response against self-antigens, such as ribonucleoproteins, in autoimmunity but also during successful cancer immunotherapy. This has important implications for the design of future cancer vaccines.

Keywords: B-cell; RNA binding protein; epitope spreading; immunotherapy; tolerance.

Publication types

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

MeSH terms

  • Autoantigens
  • Autoimmunity
  • Epitopes
  • Humans
  • Immunotherapy
  • Neoplasms* / therapy
  • T-Lymphocytes*

Substances

  • Epitopes
  • Autoantigens

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funding is acknowledged from the French Government (Agence Nationale de Recherche, ANR) through the ‘Investments for the Future’ LABEX SIGNALIFE (ANR-11-LABX-0028-01 and IDEX UCAJedi ANR-15-IDEX-01) and RNPVAX (ANR-23-CE17-0011-01, ANR-23-CE17-0011-02, ANR-23-CE17-0011-03), Canceropole PACA; Région Sud, CNRS, Université Paris Cité, INSERM cancer; INCA Plan Cancer; ITMO Cancer.