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ICOS-L as a Potential Therapeutic Target for Cancer Immunotherapy

[ Vol. 19 , Issue. 11 ]

Author(s):

Oliviero Marinelli, Massimo Nabissi*, Maria Beatrice Morelli, Luciana Torquati, Consuelo Amantini and Giorgio Santoni   Pages 1107 - 1113 ( 7 )

Abstract:


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.

Keywords:

ICOS-L, ICOS, CD275, CD278, B7, Tregs, cancer.

Affiliation:

School of Pharmacy, University of Camerino, Camerino (MC), School of Pharmacy, University of Camerino, Camerino (MC), School of Pharmacy, University of Camerino, Camerino (MC), University of Exeter Medical School, Exeter, School of Bioscience and Veterinary Medicine, University of Camerino, Camerino (MC), School of Pharmacy, University of Camerino, Camerino (MC)

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