In human, CD27 is exclusively expressed in the lymphoid lineage, in other words, by T, B and NK cells and their immediate precursors. In the mouse, CD27 is additionally expressed on early hematopoietic precursors. Importantly, CD27 is already present on naive CD4+ and CD8+ T cells. Most other co-stimulatory TNFRs are only synthesized after T cell activation. Upon activation, naive CD4+ and CD8+ T cells transiently upregulate the expression of CD27. Activated T cells proteolytically shed CD27 from the cell surface, thereby giving rise to circulating soluble CD27 that can serve as a diagnostic marker of T-cell activation. Terminally differentiated effector CD8+ T cells loose CD27, while long-lived central memory cells retain it.
CD70 / CD27L / TNFSF7 is constitutively expressed on medullary thymic epithelial cells (mTECs) in human and mouse and on certain unconventional APCs in the mouse intestine. Apart from that, CD70 / CD27L / TNFSF7 is exclusively expressed after immune activation. It is found on activated DCs, B cells, conventional- and regulatory T cells and NK cells. CD70 / CD27L / TNFSF7 expression is highly regulated by antigen, since it is under control of PRRs, T cell and B cell antigen receptors and its expression is further tuned by cytokines such as IL-1α, IL-12, TNFα, prostaglandin E2 and by CD28- and CD40 co-stimulation. Epithelial cells and other cell types may acquire CD70 / CD27L / TNFSF7 upon malignant transformation.
The CD27 & CD70 immune checkpoint pathway plays an important role in immune regulation. At an early stage, human CD27 was recognized as a T-cell co-stimulatory receptor using in vitro assays with anti-CD27 mAb. Upon its cloning, the CD27 ligand CD70 / CD27L / TNFSF7 was likewise shown to promote TCR/CD3-induced proliferation of naïve CD4+ and CD8+ human T cells and the generation of effector cells. The co-stimulatory function of CD27 was subsequently solidified by studies in CD27−/− mice and by treating wild-type mice with CD70 / CD27L / TNFSF7 blocking mAb or recombinant soluble CD70 / CD27L / TNFSF7 in infection- and immunization models.
Koen van de Ven et al. Targeting the T-cell co-stimulatory CD27/CD70 pathway in cancer immunotherapy: rationale and potential. Immunotherapy (2015) 7(6), 655–667
|Co-inhibitory immune checkpoint pathways||Co-stimulatory immune checkpoint pathways|
|PD1 & PD-L1 immune checkpoint pathway||CD40 & CD40L immune checkpoint pathway|
|CTLA-4 & CD80 (CD86) immune checkpoint pathway||OX40 & OX40L immune checkpoint pathway|
|B7-H3 / CD276 immune checkpoint pathway||HVEM & LIGHT immune checkpoint pathway|
|B7-H4 / B7S1 / B7x immune checkpoint pathway||CD28 & CD80 (CD86) immune checkpoint pathway|
|HVEM & BTLA immune checkpoint pathway||GITR & GITR Ligand immune checkpoint pathway|
|HVEM & CD160 immune checkpoint pathway||CD266 & CD155 immune checkpoint pathway|
|LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway||4-1BB & 4-1BBL immune checkpoint pathway|
|Galectin-9 & TIM-3 immune checkpoint pathway||ICOS & ICOS Ligand immune checkpoint pathway|
|Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway|
|VISTA / B7-H5 / GI24 immune checkpoint pathway|
|CEACAM1 / CD66a immune checkpoint pathway|
|SIRP alpha & CD47 immune checkpoint pathway|
|2B4 & CD48 immune checkpoint pathway|
|TIGIT & CD155 immune checkpoint pathway|