Understanding how combinatorial targeting of TLRs and TNFR family costimulatory members promote enhanced T cell responses

• Published in: Expert opinion on biological therapy Vol. 18; no. 10; p. 1073
• Main Authors: Shinde, Paurvi, Bharat, Vinita, Rodriguez-Oquendo, Annabelle, Zhou, Beiyan, Vella, Anthony T
• Format: Journal Article
• Language: English
• Published: England 03.10.2018
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Vaccines - pharmacology; Combined Modality Therapy; Drug Delivery Systems - methods; Humans; Immunity, Cellular - drug effects; Lymphocyte Activation - drug effects; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Toll-Like Receptors - antagonists & inhibitors; Toll-Like Receptors - immunology; signaling pathways; vaccines; T cell responses; TNFR family costimulatory receptors; infectious diseases; TLR adjuvants; cancer; tumor therapy
• ISSN: 1744-7682
• DOI: 10.1080/14712598.2018.1518422

Due to the ability of pathogen-associated molecular patters and tumor necrosis factor receptor (TNFR) family costimulatory agonists to boost T cell responses, studies have combined Toll-like receptor (TLR) ligands with TNFR family costimulatory receptor agonists to induce impressive and long-lasting T cell responses. Although some studies have determined how these combinatorial vaccines promote enhanced T cell responses, much remains unknown about the mechanism used by these combinations to promote synergistic T cell responses - especially in settings of infectious diseases or cancer. In this review, we look in detail at the signaling pathways induced by combinatorial targeting of TLR and TNFR family costimulatory members that help them promote synergistic T cell responses. Understanding this can greatly aid the development of novel vaccine regimens that promote cellular immune responses, which is essential for treating certain infectious diseases and cancer. Vaccines against some infectious diseases as well as therapeutic cancer vaccines require cellular immunity. Therefore, we evaluate here how signaling pathways induced by TLR ligand and costimulatory agonist combinations promote enhanced T cell responses during immunization with model antigens, viral pathogens, or tumor antigens. Once pathways that drive these combinatorial vaccines to boost T cell activation are identified, they can be incorporated in vaccines designed to target pathogens or cancer.