The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity
| Autor: | Vijay K. Kuchroo, Alexandra Schnell, Asaf Madi, Lloyd Bod |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Autoimmunity Cancer immunotherapy Review Article Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Immune system TIGIT T-Lymphocyte Subsets Immunity Neoplasms Tumor Microenvironment medicine Animals Humans Receptor Molecular Biology 030304 developmental biology Autoimmune disease 0303 health sciences Tumor microenvironment Correction Cell Biology Immunotherapy Immune Checkpoint Proteins medicine.disease Checkpoint signalling 030220 oncology & carcinogenesis Cancer research Tumour immunology |
| Zdroj: | Cell Research |
| ISSN: | 1748-7838 1001-0602 |
| Popis: | Co-inhibitory receptors are important regulators of T-cell function that define the balance between tolerance and autoimmunity. The immune regulatory function of co-inhibitory receptors, including CTLA-4, PD-1, TIM-3, TIGIT, and LAG-3, was first discovered in the setting of autoimmune disease models, in which their blockade or deficiency resulted in induction or exacerbation of the disease. Later on, co-inhibitory receptors on lymphocytes have also been found to influence outcomes in tumor and chronic viral infection settings. These receptors suppress T-cell function in the tumor microenvironment (TME), thereby making the T cells dysfunctional. Based on this observation, blockade of co-inhibitory receptors (also known as checkpoint molecules) has emerged as a successful treatment option for a number of human cancers. However, severe autoimmune-like side effects limit the use of therapeutics that block individual or combinations of co-inhibitory receptors for cancer treatment. In this review we provide an overview of the role of co-inhibitory receptors in autoimmunity and anti-tumor immunity. We then discuss current approaches and future directions to leverage our knowledge of co-inhibitory receptors to target them in tumor immunity without inducing autoimmunity. |
| Databáze: | OpenAIRE |
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