Dual blockage of both PD-L1 and CD47 enhances the therapeutic effect of oxaliplatin and FOLFOX in CT-26 mice tumor model
Reza Alimohammadi, Ghanbar Mahmoodi Chalbatani, Masoumeh Alimohammadi, Haniyeh Ghaffari‐Nazari, Arezou Rahimi, Esmail Mortaz, Nariman Mossafa, Louis Boon, Seyed Amir Jalali
Abstract
Colorectal 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.