Targeting Semaphorin 4D in Cancer: A Look from Different Perspectives

Luca Tamagnone, Giulia Franzolin

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)5146-5148
Number of pages3
JournalCancer Research
Issue number20
Publication statusPublished - Oct 15 2019


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