Great strides have been made in the immunotherapy of cancer with personalized cancer vaccines, check point inhibitory monoclonal antibodies, monoclonal antibodies that target receptors commonly expressed on Tregulatory cells, Antibody Drug Conjugates, bispecific T cell engagers (BiTEs), and combination therapies such as cancer vaccines or radiotherapy coupled with check point inhibitors.

This proposed research topic builds on what we have learned from the immune activation realized in the diverse approaches to treat cancer to, reciprocally, induce immune tolerance in the context of autoimmunity and transplantation. Recognizing that “magic bullet” approaches no more apply to treatment of cancer than to autoimmunity, this edition will emphasize strategies that involve treatments that target critical points in the immune cascade resulting in disease.

Highly effective, potentially curative therapies to induce immune tolerance in the setting of autoimmunity and transplantation that do not require long term immune suppression with consequent risks of infection and development of malignancies are under increasing development based on an expanded understanding of mechanisms mediating disease. This Research Topic embraces novel therapeutic approaches to immune tolerance based on what has been gleaned regarding immune activation and efficacy of cancer immunotherapy.

• Immune checkpoint inhibition: can we signal through CPIs to enhance immune suppression/tolerance in the settings of Autoimmunity and Transplantation? PD-1, CTLA-4, LAG-3, TIGIT etc agonist stimulation alone, in combination with several CPI agonists or in combination with complementary modalities.

• CRISPR-Cas9 based treatment to inactivate T cells expressing TCRs specific for autoantigens; application to tolerance in the setting of severe adverse events from autoimmune disease induced by cancer immunotherapy.

• Tregulatory cells specific for target autoantigens or TCR of Teffector cells mediating autoimmune/transplantation responses.

• Antigen specific approaches to immune tolerance including vaccination for induction of tolerogenic dendritic cells and activation of Tregulatory cells in vivo.

• Inhibition of epitope spreading in early phases of autoimmune disease and transplantation responses.

• Targeted cytokine or anti-cytokine therapy to induce regulatory T cells in tissues undergoing autoimmune attack or transplant rejection

Article types: Original research, Original Research, Systematic Review, Methods, Review, Policy and Practice Reviews, Hypothesis & Theory, Clinical Trial, Classification, Technology and Code, Study Protocol, Mini Review, Perspective, Case Report, Conceptual Analysis, Curriculum, Instruction, and Pedagogy, Brief Research Report

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Frontiers in Immunology

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