Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights

Frontiers in Oncology

Oncology

Robert E. Martell¹  Matthew D. Vesely²  Kathleen M. Mahoney³  J. Louise Lines⁴  Dhanya K. Nambiar⁵  Jerome Boyd-Kirkup⁶  Randolph J. Noelle⁷  Thierry Guillaudeux⁸  Andrew M. Scott⁹  Lionel D. Lewis^1,10  Sam W. Lee^1,11 

[1] Curis, Inc., Lexington, MA, United States;Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, United States;Department of Dermatology, Yale School of Medicine, New Haven, CT, United States;Department of Medical, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States;Department of Microbiology and Immunology, Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH, United States;Department of Radiation Oncology, Stanford School of Medicine, Stanford, CA, United States;Hummingbird Bioscience, Houston, TX, United States;ImmuNext Inc., Lebanon, NH, United States;Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States;Kineta Inc., Seattle, WA, United States;Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia;Department of Molecular Imaging and Therapy, Austin Health and Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia;Section of Clinical Pharmacology, Department of Medicine, Geisel School of Medicine at Dartmouth and Dartmouth Cancer Center, Hanover, NH, United States;Yale University School of Medicine, New Haven, CT, United States;

关键词: VISTA;    checkpoint inhibitors (ICIs);    immunotherapy;    PD-1;    myeloid;    immune checkpoint;    immuno-oncology (IO);   

DOI  :  10.3389/fonc.2023.1225081

 received in 2023-05-18, accepted in 2023-08-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Immune checkpoints limit the activation of the immune system and serve an important homeostatic function but can also restrict immune responses against tumors. Inhibition of specific immune checkpoint proteins such as the B7:CD28 family members programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has transformed the treatment of various cancers by promoting the anti-tumor activation of immune cells. In contrast to these effects, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) regulates the steady state of the resting immune system and promotes homeostasis by mechanisms distinct from PD-1 and CTLA-4. The effects of VISTA blockade have been shown to include a decrease in myeloid suppression coupled with proinflammatory changes by mechanisms that are separate and distinct from other immune checkpoint proteins; in some preclinical studies these immune effects appear synergistic. Given the potential benefits of VISTA blockade in the context of cancer therapy, the second Annual VISTA Symposium was convened virtually on September 23, 2022, to review new research from investigators and immuno-oncology experts. Discussions in the meeting extended the knowledge of VISTA biology and the effects of VISTA inhibition, particularly on cells of the myeloid lineage and resting T cells, as three candidate anti-VISTA antibodies are in, or nearing, clinical development.

【 授权许可】

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Copyright © 2023 Noelle, Lines, Lewis, Martell, Guillaudeux, Lee, Mahoney, Vesely, Boyd-Kirkup, Nambiar and Scott