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

J Cell Physiol. 2019 Nov;234(11):19866-19874. doi: 10.1002/jcp.28585. Epub 2019 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Drug Synergism
  • Female
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Mice, Inbred BALB C
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Spleen / drug effects
  • Spleen / pathology
  • Survival Analysis
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • Programmed Cell Death 1 Receptor
  • Oxaliplatin