Interplay between CD28 and PD-1 in T cell immunotherapy

Zuhayr Jafri; Jingwen Zhang; Connor H O'Meara; Anthony M Joshua; Christopher R Parish; Levon M Khachigian

doi:10.1016/j.vph.2024.107461

Interplay between CD28 and PD-1 in T cell immunotherapy

Vascul Pharmacol. 2024 Dec 27:107461. doi: 10.1016/j.vph.2024.107461. Online ahead of print.

Authors

Zuhayr Jafri¹, Jingwen Zhang¹, Connor H O'Meara², Anthony M Joshua³, Christopher R Parish⁴, Levon M Khachigian⁵

Affiliations

¹ Vascular Biology and Translational Research, Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
² Vascular Biology and Translational Research, Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia; Division of Head & Neck Oncology and Microvascular Reconstruction, Department of Otolaryngology, Head & Neck Surgery, University of Virginia Health Services, Charlottesville, VA 22903, USA; Department of Otolaryngology, Head & Neck Surgery, Australian National University, Acton, ACT 0200, Australia.
³ Kinghorn Cancer Centre, St Vincents Hospital, Sydney and Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Cancer and Vascular Biology Group, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
⁵ Vascular Biology and Translational Research, Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: [email protected].

PMID: 39734005
DOI: 10.1016/j.vph.2024.107461

Abstract

Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionized the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and vice versa). CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion. We also consider clinical attempts at targeting CD28; the challenges faced by past attempts and recent promising developments.

Keywords: CD28; Immunotherapy; PD-1; T cell.

Publication types

Review