Interplay between CD28 and PD-1 in T cell immunotherapy.

Vascul Pharmacol

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:

Published: December 2024

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.

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http://dx.doi.org/10.1016/j.vph.2024.107461DOI Listing

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