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Synergistic antitumor effect of anti-PD-L1 combined with oxaliplatin on a mouse tumor model
Authors:Soheila Golchin  Reza Alimohammadi  Mohammad Rostami Nejad  Seyed Amir Jalali
Affiliation:1. Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:Oxaliplatin (OXP) can change tumor microenvironment from immune-suppressive toward the immune-favorable condition. Almost all of the antitumor agents cannot totally cure cancer as monotherapy. So the current focus of cancer research became combining therapy using different treatment regimen, especially chemotherapy with checkpoint blockers. In this study, we assessed the activity of combining regimen using anti-PD-L1 with OXP in CT26 tumor-bearing BALB/c mice. We further analyzed the immune cell phenotypes in tumor site, lymph nodes, and spleen by flow cytometry analysis. Our study showed that combination therapy with OXP and anti-PD-L1 significantly increased survival in vivo and inhibited tumor growth of tumor-bearing mice. Inconsistent with better antitumor activity, our combination therapy led to an increase in tumor-infiltrating activated CD8+ T cells. In draining lymph nodes and spleen, regulatory T cells decreased significantly. Mice receiving either anti-PD-L1 or OXP alone had a larger tumor and lower survival rate in comparison with combination therapy receiving group. The time and order of administration of each component of the combination therapy affected antitumor response.
Keywords:anti-PD-L1  cancer  chemotherapy  combination therapy  immunotherapy
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