The evolutionary legacy of immune checkpoint inhibitors. (November 2022)

• Record Type: Journal Article
• Authors: Kaushik, Itishree; Ramachandran, Sharavan; Zabel, Carson; Gaikwad, Shreyas; Srivastava, Sanjay K.
• Is Part Of: Seminars in cancer biology. Volume 86(2023)Part 2
• Page Start: 491
• Page End: 498
• Publication Date: 2022-11
• Subjects: ICIs Immune checkpoint inhibitors -- CTLA4 Cytotoxic T lymphocyte-associated protein 4 -- PD-1 Programmed cell death-1 -- PD-L1 Programmed cell death Ligand-1 -- TME Tumor microenvironment -- APCs Antigen presenting cells -- MHC Major histocompatibility complex -- BTLA B and T lymphocyte attenuator -- Tregs Regulatory T cells -- ICT Immune checkpoint therapy -- TH1 Helper T cell 1 -- LAG-3 Lymphocyte Activation Gene-3 -- TIL Tumor infiltrating lymphocytes -- DLT Dose limiting toxicity -- PR Partial Response -- CR Complete Response -- ORR Overall response rate -- DCR Disease control rate -- DCT Decentralized clinical trials -- DCs Dendritic Cells -- RCC Renal cell carcinoma -- CRC Colorectal cancer -- NSCLC Non-small cell lung cancer -- AEs Adverse events -- ADC Antibody-drug conjugate -- SCLC Small cell lung cancer -- CRPC Castrate-resistant prostate cancer -- NKG Natural killer group -- HNSCC Head and neck squamous cell carcinomas -- OS Overall survival -- ATP Adenosine triphosphate -- TAMs Tumor associated macrophages -- MDSCs Myeloid-derived suppressor cells -- TNBC Triple negative breast cancer -- PVRIG Poliovirus receptor-related immunoglobulin domain containing -- PVRL2 Poliovirus receptor-related 2; PD-1/PD-L1 -- CTLA-4 -- Tumor microenvironment -- Antigen presenting cells; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2022.03.020
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Immune check point inhibitors (ICIs) have marked their existence in the field of cancer immunotherapy. Their existence dates to 2011 when the first anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) got its FDA approval for the management of metastatic melanoma. The class of ICIs now also include antibodies against programmed cell death-1 (PD-1) and its ligand (PD-L1) which immediately gained FDA approval for use against multiple cancer types because of their effect on patient survival. These discoveries were followed by a significant rise in the identification of novel ICIs with potential anti-tumor response. Researchers have identified various novel checkpoint inhibitors which are currently under clinical trials. Despite the success of ICIs, only a small subset of patients with specific tumor types achieves a promising response. Not only efficient therapeutic response but also development of resistance, recurrence and other immune-related adverse effects limit the applicability of immune checkpoint inhibitors. These challenges can only be addressed when a directed approach is implemented at both basic and translational level. In this review, we have briefly discussed the history of ICIs, the next generation of inhibitors which are currently under clinical trial and mechanisms of resistance that can lead to treatment failure. Ultimately, by combining these insights researchers might be able to achieve a more durable and effective response in cancer patients.