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The tumor necrosis factor receptor superfamily (TNFRSF) is a pivotal immunoregulatory group of receptors involved in almost all aspects of immunity. Signaling by TNFRSF members has a multifactorial impact on the development and efficacy of anti-cancer immunity and on cancer cells directly. For instance, the role of the TNFRSF in immunity includes the CD40-/CD40L-mediated critical licensing step of dendritic cell-mediated activation of T cells, GITR-/GITRL-mediated development of regulatory T cell function and 4-1BB−/4-1BBL-mediated co-stimulation of cytotoxic T cells after MHC/TCR interaction. Therapeutic activation of signaling by TNFRSF members is a major focus within oncology and cancer immunology with a range of therapeutics being developed to exploit signaling by this family, including monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and ligand-based targeting approaches. In this chapter, we highlight a select group of TNFRSF members, specifically CD40, 4-1BB, CD27, OX40, and GITR, that have gained prominence in cancer immunotherapy and provide a description of recent insights into biology followed by a review of cutting-edge TNFRSF signaling-based cancer immunotherapeutics.

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Advances in Therapeutic Targeting of the Tumor Necrosis Factor Receptor Superfamily Members for Cancer Immunotherapy

  • 工具书词条

  • 发表日期：

    2025年

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  • Martijn Vlaming,
  • Yuan He,
  • Edwin Bremer

摘要

The tumor necrosis factor receptor superfamily (TNFRSF) is a pivotal immunoregulatory group of receptors involved in almost all aspects of immunity. Signaling by TNFRSF members has a multifactorial impact on the development and efficacy of anti-cancer immunity and on cancer cells directly. For instance, the role of the TNFRSF in immunity includes the CD40-/CD40L-mediated critical licensing step of dendritic cell-mediated activation of T cells, GITR-/GITRL-mediated development of regulatory T cell function and 4-1BB−/4-1BBL-mediated co-stimulation of cytotoxic T cells after MHC/TCR interaction. Therapeutic activation of signaling by TNFRSF members is a major focus within oncology and cancer immunology with a range of therapeutics being developed to exploit signaling by this family, including monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and ligand-based targeting approaches. In this chapter, we highlight a select group of TNFRSF members, specifically CD40, 4-1BB, CD27, OX40, and GITR, that have gained prominence in cancer immunotherapy and provide a description of recent insights into biology followed by a review of cutting-edge TNFRSF signaling-based cancer immunotherapeutics.