TY - JOUR
T1 - Targeting Semaphorin 4D in Cancer
T2 - A Look from Different Perspectives
AU - Tamagnone, Luca
AU - Franzolin, Giulia
N1 - ©2019 American Association for Cancer Research.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - Semaphorin 4D (Sema4D) plays a role in various cell types including B lymphocytes, differentiating neurons, endothelial cells, and cancer cells. Preclinical and in vitro studies have shown that Sema4D-directed antibodies in combination with immune checkpoint inhibitors reshape the tumor microenvironment by promoting recruitment of effector lymphocytes and antigen-presenting cells, while reducing immunosuppressive cell types, which ultimately leads to tumor rejection. Hence, early-stage clinical trials with combination therapies including anti-Sema4D antibodies are ongoing. In this issue of Cancer Research, Zuazo-Gaztelu and colleagues report an unexpected proinvasive effect induced by anti-Sema4D antibodies in a preclinical model of neuroendocrine pancreatic cancer (Rip1-Tag2), mediated by retrograde signaling of transmembrane Sema4D in macrophages, which increases their recruitment to tumors, SDF-1 secretion, and metastasis-promoting phenotype.See related article by Zuazo-Gaztelu et al., p. 5328.
AB - Semaphorin 4D (Sema4D) plays a role in various cell types including B lymphocytes, differentiating neurons, endothelial cells, and cancer cells. Preclinical and in vitro studies have shown that Sema4D-directed antibodies in combination with immune checkpoint inhibitors reshape the tumor microenvironment by promoting recruitment of effector lymphocytes and antigen-presenting cells, while reducing immunosuppressive cell types, which ultimately leads to tumor rejection. Hence, early-stage clinical trials with combination therapies including anti-Sema4D antibodies are ongoing. In this issue of Cancer Research, Zuazo-Gaztelu and colleagues report an unexpected proinvasive effect induced by anti-Sema4D antibodies in a preclinical model of neuroendocrine pancreatic cancer (Rip1-Tag2), mediated by retrograde signaling of transmembrane Sema4D in macrophages, which increases their recruitment to tumors, SDF-1 secretion, and metastasis-promoting phenotype.See related article by Zuazo-Gaztelu et al., p. 5328.
U2 - 10.1158/0008-5472.CAN-19-2387
DO - 10.1158/0008-5472.CAN-19-2387
M3 - Article
C2 - 31615809
VL - 79
SP - 5146
EP - 5148
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 20
ER -