Innate Immune Checkpoint Inhibitors: The Next Breakthrough in Medical Oncology?
Autor: | Robert W. Lentz, Siddhartha Mitra, Meryl D. Colton, Wells A. Messersmith |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Antigen presentation chemical and pharmacologic phenomena Medical Oncology Article 03 medical and health sciences 0302 clinical medicine Immune system TIGIT Neoplasms Humans Medicine CD155 Immune Checkpoint Inhibitors Innate immune system biology business.industry Immunotherapy biochemical phenomena metabolism and nutrition Acquired immune system 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Antibody business |
Zdroj: | Mol Cancer Ther |
ISSN: | 1538-8514 1535-7163 |
Popis: | While immunotherapy has revolutionized the treatment of many types of advanced cancer, most patients still do not derive benefit. The currently available immune checkpoint inhibitors target the adaptive immune system, generating a T-cell antitumor response. However, an antitumor immune response depends on a complex interplay of both innate and adaptive immune cells. The innate immune system is a promising new target, and innate immune checkpoint inhibitors can disrupt inhibitory interactions (“don't eat me” signals) between tumor and both phagocytes and natural killer cells. The checkpoint inhibitor may also provide a stimulatory interaction (“eat me” signal), or this can be achieved through use of combination therapy. This generates antitumor effector functions including phagocytosis, natural cytotoxicity, antibody-dependent effects, and synergistic activation of the adaptive immune system via antigen presentation. This is a rapidly expanding area of drug development, either alone or in combination (with anticancer antibodies or adaptive immune checkpoint inhibitors). Here, we comprehensively review the mechanism of action and up-to-date solid tumor clinical trial data of the drugs targeting phagocytosis checkpoints (SIRPα/CD47, LILRB1/MHC-I, and LILRB2/MHC-I) and natural killer–cell checkpoints (TIGIT/CD112 + CD155, PVRIG/CD112, KIRs/MHC-I, and NKG2A-CD94/HLA-E). Innate immune checkpoint inhibitors could once again revolutionize immune-based cancer therapies. |
Databáze: | OpenAIRE |
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