TY - JOUR
T1 - New emerging targets in cancer immunotherapy: The role of GITR
AU - Buzzatti, Giulia
AU - Dellepiane, Chiara
AU - Del Mastro, Lucia
PY - 2020/8/18
Y1 - 2020/8/18
N2 - In the last decade, immunotherapies have revolutionised anticancer treatment. However, there is still a number of patients that do not respond or acquire resistance to these treatments. Despite several efforts to combine immunotherapy with other strategies like chemotherapy, or other immunotherapy, there is an â € urgent' need to better understand the immune landscape of the tumour microenvironment. New promising approaches, in addition to blocking co-inhibitory pathways, such those cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 mediated, consist of activating co-stimulatory pathways to enhance antitumour immune responses. Among several new targets, glucocorticoid-induced TNFR-related gene (GITR) activation can promote effector T-cell function and inhibit regulatory T-cell (Treg) function. Preclinical data on GITR-agonist monoclonal antibodies (mAbs) demonstrated antitumour activity in vitro and in vivo enhancing CD8 + and CD4 + effector T-cell activity and depleting tumour-infiltrating Tregs. Phase I clinical trials reported a manageable safety profile of GITR mAbs. However, monotherapy seems not to be effective, whereas responses have been reported in combination therapy, in particular adding PD-1 blockade. Several clinical studies are ongoing and results are awaited to further develop GITR-stimulating treatments.
AB - In the last decade, immunotherapies have revolutionised anticancer treatment. However, there is still a number of patients that do not respond or acquire resistance to these treatments. Despite several efforts to combine immunotherapy with other strategies like chemotherapy, or other immunotherapy, there is an â € urgent' need to better understand the immune landscape of the tumour microenvironment. New promising approaches, in addition to blocking co-inhibitory pathways, such those cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 mediated, consist of activating co-stimulatory pathways to enhance antitumour immune responses. Among several new targets, glucocorticoid-induced TNFR-related gene (GITR) activation can promote effector T-cell function and inhibit regulatory T-cell (Treg) function. Preclinical data on GITR-agonist monoclonal antibodies (mAbs) demonstrated antitumour activity in vitro and in vivo enhancing CD8 + and CD4 + effector T-cell activity and depleting tumour-infiltrating Tregs. Phase I clinical trials reported a manageable safety profile of GITR mAbs. However, monotherapy seems not to be effective, whereas responses have been reported in combination therapy, in particular adding PD-1 blockade. Several clinical studies are ongoing and results are awaited to further develop GITR-stimulating treatments.
KW - cancer
KW - GITR
KW - immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=85089769111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089769111&partnerID=8YFLogxK
U2 - 10.1136/esmoopen-2020-000738
DO - 10.1136/esmoopen-2020-000738
M3 - Review article
C2 - 32817129
AN - SCOPUS:85089769111
VL - 4
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
M1 - e000738
ER -