CD27, a member of the tumour necrosis factor receptor superfamily (TNFRSF7), plays a crucial role in the immune system [2,3,4,6]. It functions as a co-stimulatory molecule for T-cells, B-cells, and NK-cells. The interaction of CD27 with its ligand CD70 is essential for T-cell memory fate determination, and also impacts T-cell activation, proliferation, and differentiation into effector and memory T-cells [1,2,3,6]. This pathway is involved in multiple biological processes, such as antiviral immunity, cancer immunity, and autoimmune disease pathogenesis [2,3,4].

In mice, co-stimulation of CD8+ T-cells through CD27 promotes immune activation and enhances primary, secondary, memory, and recall responses towards viral infections [3]. Chronic CD27-CD70 costimulation in vivo promotes type 1-specific polarization of effector Tregs, which may regulate the development of Th1 immunity and the switch to long-term memory [7]. Blockade of the CD27-CD70 pathway has been shown to ameliorate disease manifestations in animal models of autoimmune diseases like murine collagen-induced arthritis and experimental colitis [4].

In conclusion, CD27 is a key co-stimulatory immune-checkpoint receptor. Its functions, revealed through in vivo studies including those with mouse models, have significant implications in antiviral, anti-tumour, and autoimmune immunotherapies. The manipulation of the CD27-CD70 pathway shows potential as a therapeutic strategy in these disease areas [2,3,4,5].

References:

1. Jaeger-Ruckstuhl, Carla A, Lo, Yun, Fulton, Elena, Furlan, Scott N, Riddell, Stanley R. . Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks. In Immunity, 57, 287-302.e12. doi:10.1016/j.immuni.2024.01.011. https://pubmed.ncbi.nlm.nih.gov/38354704/

2. Starzer, Angelika M, Berghoff, Anna S. . New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). In ESMO open, 4, e000629. doi:10.1136/esmoopen-2019-000629. https://pubmed.ncbi.nlm.nih.gov/32152062/

3. Grant, Emma J, Nüssing, Simone, Sant, Sneha, Clemens, E Bridie, Kedzierska, Katherine. 2017. The role of CD27 in anti-viral T-cell immunity. In Current opinion in virology, 22, 77-88. doi:10.1016/j.coviro.2016.12.001. https://pubmed.ncbi.nlm.nih.gov/28086150/

4. Han, Bobby Kwanghoon, Olsen, Nancy J, Bottaro, Andrea. 2015. The CD27-CD70 pathway and pathogenesis of autoimmune disease. In Seminars in arthritis and rheumatism, 45, 496-501. doi:10.1016/j.semarthrit.2015.08.001. https://pubmed.ncbi.nlm.nih.gov/26359318/

5. Lutfi, Forat, Wu, Long, Sunshine, Sarah, Cao, Xuefang. 2021. Targeting the CD27-CD70 Pathway to Improve Outcomes in Both Checkpoint Immunotherapy and Allogeneic Hematopoietic Cell Transplantation. In Frontiers in immunology, 12, 715909. doi:10.3389/fimmu.2021.715909. https://pubmed.ncbi.nlm.nih.gov/34630390/

6. Borst, Jannie, Hendriks, Jenny, Xiao, Yanling. . CD27 and CD70 in T cell and B cell activation. In Current opinion in immunology, 17, 275-81. doi:. https://pubmed.ncbi.nlm.nih.gov/15886117/

7. Bowakim-Anta, Natalia, Acolty, Valérie, Azouz, Abdulkader, Oldenhove, Guillaume, Moser, Muriel. 2023. Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs. In Frontiers in immunology, 14, 1023064. doi:10.3389/fimmu.2023.1023064. https://pubmed.ncbi.nlm.nih.gov/36993956/