Cytotoxicity as a form of immunogenic cell death leading to efficient tumor antigen cross‐priming

Author:

Luri‐Rey Carlos1,Gomis Gabriel1,Glez‐Vaz Javier1ORCID,Manzanal Almudena1,Martinez Riaño Ana1,Rodriguez Ruiz Maria E.2,Teijeira Alvaro123,Melero Ignacio12345ORCID

Affiliation:

1. Program of Immunology and Immunotherapy Cima Universidad de Navarra Pamplona Spain

2. Department of Oncology Clinica Universidad de Navarra Pamplona Spain

3. Navarra Institute for Health Research (IDISNA) Pamplona Spain

4. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid Spain

5. Department of Immunology and Immunotherapy Clínica Universidad de Navarra Pamplona Spain

Abstract

SummaryAntigen cross‐priming of CD8+ T cells is a critical process necessary for the effective expansion and activation of CD8+ T cells endowed with the ability to recognize and destroy tumor cells. The cross‐presentation of tumor antigens to cross‐prime CD8+ T cells is mainly mediated, if not only, by a subset of professional antigen‐presenting cells termed type‐1 conventional dendritic cells (cDC1). The demise of malignant cells can be immunogenic if it occurs in the context of premortem stress. These ways of dying are termed immunogenic cell death (ICD) and are associated with biochemical features favoring cDC1 for the efficient cross‐priming of tumor antigens. Immunosurveillance and the success of immunotherapies heavily rely on the ability of cytotoxic immune cells, primarily CD8+ T cells and NK cells, to detect and eliminate tumor cells through mechanisms collectively known as cytotoxicity. Recent studies have revealed the significance of NK‐ and CTL‐mediated cytotoxicity as a prominent form of immunogenic cell death, resulting in mechanisms that promote and sustain antigen‐specific immune responses. This review focuses on the mechanisms underlying the cross‐presentation of antigens released during tumor cell killing by cytotoxic immune cells, with an emphasis on the role of cDC1 cells. Indeed, cDC1s are instrumental in the effectiveness of most immunotherapies, underscoring the significance of tumor antigen cross‐priming in contexts of immunogenic cell death. The notion of the potent immunogenicity of cell death resulting from NK or cytotoxic T lymphocyte (CTL)‐mediated cytotoxicity has far‐reaching implications for cancer immunotherapy.

Funder

Ministerio de Ciencia e Innovación

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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