title: The risks of targeting co-inhibitory pathways to modulate pathogen-directed T cell responses.
abstract: The identification of T cell co-inhibition as a central mechanism in the regulation of adaptive immunity during infectious diseases provides new opportunities for immunotherapeutic interventions. However, the fact that T cell activity is frequently downregulated during pathogen-directed responses suggests a pivotal physiological role of co-inhibitory pathways during infectious disease. Reports of exacerbated immunopathology in conditions of impaired co-inhibition foster the view that downregulation of T cell activity is an essential negative feedback mechanism that protects from excessive pathogen-directed immunity. Thus, targeting co-inhibitory pathways can bear detrimental potential through the deregulation of physiological processes. Here, we summarize recent preclinical and clinical interventions that report immune-related adverse events after targeting co-inhibitory pathways.
authors: Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.
authors: Helge
authors: H
authors: Frebel
authors: Annette
authors: A
authors: Oxenius
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D007239:Infections / Q000150:complications* / Q000276:immunology / Q000628:therapy; D058990:Molecular Targeted Therapy / Q000009:adverse effects* / Q000379:methods; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D020239:Receptor Cross-Talk / Q000187:drug effects; D015163:Superinfection / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor