Blocking CD47-SIRPα Signal Axis as Promising Immunotherapy in Ovarian Cancer

Abstract

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.

CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features

“…CD47 had become a star anti-tumor molecule since its immune checkpoint (IC) identity was revealed [ 12 ]. Initially, CD47 was known as integrin-associated protein involved in inflammatory cell chemotaxis, adhesion, migration, and activation of anti-inflammatory response and platelets.…”

“…Adaptive immunity may play a key role in this prognostic-protective effect, including activation and increased levels of cytotoxic T cells and TICs [ 36 , 37 ]. Previous studies have demonstrated that simultaneously high CD47 and positive PD-L1 expression on tumor cells could synergistically promote tumor development, and that dual-blockade could achieve better anti-tumor effects than single blockade of CD47 or PD-L1 [ 12 , 38 ]. Our study might reveal a novel and more common synergistic pro-tumor immunophenotyping.…”

“…First, negative PD-L1 expression on TICs was related to suppression of adaptive immunity as mentioned [ 36 , 37 ]. Second, CD47-SIRPα signal both inhibits the innate immunity by suppression of macrophage phagocytosis and NK cells’ killing effects, and the adaptive immunity by suppression of tumor antigens cross-presentation and T cell activation [ 12 , 38 – 40 ]. The combinations of both effects created a fully immunosuppressive TME promoting EOC development.…”

“…Moreover, blocking CD47-SIRPα signal showed remarkable anti-tumor effects in preclinical trials [ 11 ]. Although the effect of CD47 on the prognosis of EOC is partially controversial, CD47 is still regarded as a potential novel target considering its high expression profile in OC and promising preclinical results [ 12 ]. Additionally, EOC presents an obvious genetic predisposition, and BRCA mutation, a prognostic protective factor, is the most common genetic pathogenic gene.…”

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

“…This suggests that CD47 may serve as an important biomarker for predicting response to immunotherapy [49,69]. Preclinical studies have demonstrated that blocking CD47 can enhance the efficacy of immunotherapy by enhancing immune cell Allows cells to evade immune surveillance [50,60,64] PI3K/Akt CD47 interacts with PI3K/Akt pathway Regulates cellular processes such as cell survival, proliferation, and migration [61,65] infiltration and inducing tumor cell death [70]. For instance, combination therapies incorporating CD47 blockade and checkpoint inhibitors have exhibited improved anti-tumor immunity and enhanced tumor regression [71].…”