Dual blockage of both PD-L1 and CD47 enhances immunotherapy against circulating tumor cells

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Dual blockage of both PD-L1 and CD47 enhances immunotherapy against circulating tumor cells


Abstract
Carcinoma metastasis is triggered by a subpopulation of circulating tumor cells (CTCs). And single immune checkpoint therapy is not good enough to inhibit CTC-induced metastasis. Here, we demonstrate that simultaneously blocking CD274 (programmed death ligand 1, PD-L1 or B7-H1) and CD47 checkpoints which were respectively signal of “don’t find me” and “don’t eat me” on CTCs by corresponding antibodies could enhance the inhibition tumor growth than single CD274 or CD47 antibody alone. In vitro flow cytometry data proved that CD47 and CD274 were overexpressed on the tested mouse tumor cell lines. The antibodies could effectively block the expressions of CD47 and CD274 on the cell surface and stably attached to tumor cell surface for several hours. The simultaneous blockade on both CD47 and CD274 checkpoints inhibited tumor growth and CTCs metastasis more potently than a single antibody inhibition or blank control on 4T1 tumor mouse model in vivo. Our results demonstrated that simultaneous dual targeting immune checkpoints, i.e., CD47 and CD274, by using specific antibodies may be more effective as an immunotherapeutics on CTCs than a CD47 or CD274 alone.



https://www.nature.com/articles/s41598-019-40241-1

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Interaction between circulating cancer cells and platelets: clinical implication


Abstract

Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells (CTCs), detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.

Keywords: Circulating tumor cells (CTCs), platelet, epithelial-mesenchymal transition (EMT), immune surveillance, metastasis


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626816/

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