Next generation of immune checkpoint therapy in cancer: new developments and challenges
By J. Marin-Acevedo, Bhagirathbhai R. Dholaria, A. Soyano, K. Knutson, S. Chumsri, Y. Lou. Journal of Hematology & Oncology, 2018
707 citations recorded by the source corpus.
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body’s immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/2fecca7ae139327e9e8108e46ad8ee9f5c78c24b
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Citations in the corpus
- Immune Checkpoint Inhibitors in Cancer Therapy (2022, background): “IDO1 is an enzyme that reduces CD8 cell activity by converting tryptophan to kynurenines, emphasising its immunosuppressive role [137].”
- Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4 (2019, background): “Immune checkpoint therapies do not kill cancer cells directly, instead they harness the power of the host’s immune system to reenhance endogenous anti-tumor activity [36].”