Next generation of immune checkpoint inhibitors and beyond

• Published in: Journal of hematology and oncology Vol. 14; no. 1; pp. 45 - 29
• Main Authors: Marin-Acevedo, Julian A, Kimbrough, ErinMarie O, Lou, Yanyan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.03.2021; BioMed Central; BMC
• Subjects: Animals; Antitumor activity; Apoptosis; B cells; Cancer; Cancer therapies; Cell death; Clinical trials; CTLA-4 protein; Cytotoxic T lymphocytes; Cytotoxicity; Health aspects; Hematology; Humans; Immune checkpoint; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immune evasion; Immune response; Immune system; Immunological tolerance; Immunotherapy; Immunotherapy - methods; Ipilimumab; Ligands; Lymphocytes; Lymphocytes T; Medical research; Monoclonal antibodies; Neoplasms - immunology; Neoplasms - therapy; Oncology; PD-1 protein; PD-L1 protein; Review; Self; T cell receptors; T cells; Tumor cells; Tumor Escape - drug effects; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumors; Immune checkpoint therapy; Tumor microenvironment; Immunotherapy; Immune evasion; Inhibitory pathways; Cytotoxic T lymphocytes; Cancer
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-021-01056-8

The immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an important role in the pathogenesis of cancer. Tumor cells evade immune recognition, in part, due to the immunosuppressive features of the tumor microenvironment. Immunotherapy augments the host immune system to generate an antitumor effect. Immune checkpoints are pathways with inhibitory or stimulatory features that maintain self-tolerance and assist with immune response. The most well-described checkpoints are inhibitory in nature and include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Molecules that block these pathways to enhance the host immunologic activity against tumors have been developed and become standard of care in the treatment of many malignancies. Only a small percentage of patients have meaningful responses to these treatments, however. New pathways and molecules are being explored in an attempt to improve responses and application of immune checkpoint inhibition therapy. In this review, we aim to elucidate these novel immune inhibitory pathways, potential therapeutic molecules that are under development, and outline particular advantages and challenges with the use of each one of them.