TY - JOUR
T1 - Dual blockage of both PD-L1 and CD47 enhances the therapeutic effect of oxaliplatin and FOLFOX in CT-26 mice tumor model
AU - Alimohammadi, Reza
AU - Mahmoodi Chalbatani, Ghanbar
AU - Alimohammadi, Masoumeh
AU - Ghaffari-Nazari, Haniyeh
AU - Rahimi, Arezou
AU - Mortaz, Esmail
AU - Mossafa, Nariman
AU - Boon, Louis
AU - Jalali, Seyed Amir
N1 - Acknowledgements
This article has been extracted from the thesis written by Mr. Reza Alimohammadi in School of Medicine Shahid Beheshti University of Medical Sciences (Registration No: 364). Ethics committee approval ID: IR. SBMU. MSP.
REC.1396.370. This work was supported by Shahid Beheshti University of Medical Sciences (Grant no: 10244).
© 2023. The Author(s).
PY - 2023/2/11
Y1 - 2023/2/11
N2 - 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.
AB - 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.
KW - Animals
KW - Mice
KW - Antibodies, Blocking
KW - B7-H1 Antigen/metabolism
KW - CD47 Antigen/metabolism
KW - Oxaliplatin/pharmacology
KW - Tomography, X-Ray Computed
KW - Tumor Microenvironment
KW - Antineoplastic Combined Chemotherapy Protocols/pharmacology
KW - Colorectal Neoplasms/drug therapy
UR - https://pubmed.ncbi.nlm.nih.gov/36774400
U2 - 10.1038/s41598-023-29363-9
DO - 10.1038/s41598-023-29363-9
M3 - Article
C2 - 36774400
SN - 2045-2322
VL - 13
SP - 2472
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -