Synergistic antitumor effect of anti‐PD‐L1 combined with oxaliplatin on a mouse tumor model

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. K E Y W O R D Santi-PD-L1, cancer, chemotherapy, combination therapy, immunotherapy

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“…These results confirmed that the antitumor efficacy is affected by both order and time of administration of each component in the combined therapy [62]. Moreover, chemotherapeutic compounds, such as oxaliplatin (OXL), can reverse the immune-suppressive state of TME into an immune-favorable one [62]. All these studies highlight that nanocarrier-mediated ICI delivery when combined with chemotherapy increase even more the antitumor efficacy of the therapy.…”

“…Both enhancement in treatment efficiency and side effects limitation can be reached with the synergic approach combining ICI nanocarrier delivery with chemotherapy. These results confirmed that the antitumor efficacy is affected by both order and time of administration of each component in the combined therapy [62]. Moreover, chemotherapeutic compounds, such as oxaliplatin (OXL), can reverse the immune-suppressive state of TME into an immune-favorable one [62].…”

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“…The cells were filtered through a 70 μm cell strainer (BD Falcon, USA) and then centrifuged at 300g for 10 min. So, the pellets of cells were suspended in flow cytometry staining buffer (phosphatebuffered saline containing 5% FBS) and analyzed by flow cytometry using fluorochrome antibodies against CD4 (clone GK1.5), CD8 (clone 53-6.7), CD25 (clone 3C7), Foxp3 (clone 150 D), and IgG1 isotype control (clone MOPC-21) (Biolegend, San Diego, California) [21].…”

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“…Further, anti-mouse PD-L1 significantly improved survival of mice implanted with CT26 CRC cells [124]. The antitumor activity of anti-PD-L1 was enhanced by combination with oxaliplatin, which resulted in increased release of high-motility group box 1 within CT26 tumors [125].…”