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.

ICOS-L as a Potential Therapeutic Target for Cancer Immunotherapy

Marinelli O;Nabissi M;Morelli MB;TORQUATI, LUCIANA EMILIA;Amantini C;Santoni G
2018-01-01

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.
2018
262
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/426088
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