Background: The co-stimulatory B7 family members are cell-surface protein ligands, binding
to receptors on lymphocytes to regulate immune responses. One of them is the inducible co-stimulatory
molecule ligand (ICOS-L). This protein is expressed on professional antigen-presenting cells (APCs),
including B cells, macrophages, and dendritic cells (DCs), but it can also be expressed by endothelial
cells, lung epithelium and in tumour microenvironment cells. ICOS-L is important for memory and effector
T cells during the specific humoral immune responses, but its role in cancer is not yet understood.
Objective: To discuss the role of ICOS/ICOS-L in cancer, given importance of identifying selective targets
for cancer treatment, and knowing the mechanism of immune evasion by tumour.
Main Findings: ICOS/ICOS-L signal has opposite effects on the T-cell response. ICOS-L is activated in
several types of cancers to maintain immunosuppressive CD4+ T cell subsets, such as regulatory T cells
(Tregs). ICOS-L over-expression is associated with tumour progression and poor overall survival. In
colon cancer, activation of this co-stimulatory signal is associated with improved survival suggesting a
dualistic effect of the ICOS/ICOs-L signal pathway. Interestingly, following anti-cancer vaccine or anti-
CTLA-4 treatment, ICOS+ T cells increased significantly in both the CD4+ and CD8+ population and the
ratio Teff/Treg increased in tumour microenvironment. This suggests a potential role of ICOS/ICOS-L
in improving effectiveness of cancer therapy.
Conclusion: ICOS/ICOS-L signal pathway has the potential to improve cancer treatment. However,
studies in other models are needed to understand whether inhibition of ICOS expression or the blockage
of its co-stimulation could be a potential therapeutic target or adjuvant treatment for immunotherapy.