Author:
Alimohammadi Reza,Mahmoodi Chalbatani Ghanbar,Alimohammadi Masoumeh,Ghaffari-Nazari Haniyeh,Rahimi Arezou,Mortaz Esmail,Mossafa Nariman,Boon Louis,Jalali Seyed Amir
Abstract
AbstractColorectal cancer is a poorly immunogenic. Such property can be reverted by using ICD. However, ICD inducers can also induce the expression of inhibitory checkpoint receptors CD47 and PD-L1 on tumor cells, making CRC tumors resistant to mainly CD8 T cell killing and macrophage-mediated phagocytosis. In this study, we examined the therapeutic effect of Oxaliplatin and FOLFOX regimen in combination with blocking antibodies against CD47 and PD-L1. FOLFOX and Oxaliplatin treatment lead to an increase in CD47 and PD-L1 expression on CT-26 cells invitro and invivo. Combining blocking antibodies against CD47 and PD-L1 with FOLFOX leads to a significant increase in survival and a decrease in tumor size. This triple combining regimen also leads to a significant decrease in Treg and MDSC and a significant increase in CD8 + INF-γ + lymphocytes and M1/M2 macrophage ratio in the tumor microenvironment. Our study showed triple combining therapy with FOLFOX, CD47 and PD-L1 is an effective treatment regimen in CT-26 mice tumor model and may consider as a potential to translate to the clinic.
Funder
School of Medicine, Shahid Beheshti University of Medical Sciences
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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