1195P - Compromised efficacy of PD-L1 blockade therapy in axenic (germ-free) mice with syngeneic tumors

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Bioethics, Legal, and Economic Issues
Cancer Immunology and Immunotherapy
Presenter Aaron Mansfield
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors A. Mansfield1, X. Liu2, S. Cao3, W. Bindeman4, P. Yin5, L. Till6, S. Harrington7, H. Dong8
  • 1Division Of Medical Oncology, Mayo Clinic, 55905 - Rochester/US
  • 2Urology And Immunology Research, Mayo Clinic, 55905 - Rochester/US
  • 3Biochemistry And Molecular Biology, Mayo Clinic, 55905 - Rochester/US
  • 4Research Services, Mayo Clinic, 55905 - Rochester/US
  • 5Medical School, Campbell University School of Osteopathic Medicine, 27546 - Lillington/US
  • 6Research, Mayo Clinic, 55905 - Rochester/US
  • 7Immunology Research, Mayo Clinic, 55905 - Rochester/US
  • 8Immunology, Mayo Clinic, 55905 - Rochester/US

Abstract

Background

The microbiome can have profound effects on the innate immune system. Since the innate immune system regulates the adaptive immune response to antigens, we hypothesized that the microbiome may influence anti-tumor responses to immune checkpoint inhibitors. Accordingly, we sought to characterize the anti-tumor effects of PD-L1 blockade therapy between mice with syngeneic tumors in conventional (specific pathogen-free, SPF) and germ-free (GF) environments.

Methods

B16-OVA or Lewis Lung Cancer (LLC) cell lines were injected subcutaneously into the flanks of 10-12 week-old C57BL/6 mice in both SPF and germ-free (axenic) environments. Mice with B16-OVA tumors in SPF (n = 6) and GF (n = 12, 6 females and 6 males) environments, and mice with LLC tumors in GF (n = 6) environments were randomized to receive the murine PD-L1 blocking antibody 10B5 or an isotype control. Tumor growth was evaluated every 2-3 days until days 35-40 when all mice were euthanized. Tumor size was compared between treatment groups in each environment at day 24 with the Mann Whitney U test. This project was approved by Mayo Clinic’s Institutional Review Board and Institutional Animal Care and Use Committee. Funding was provided by the NIH (K12 CA90628) and Mayo Clinic’s Center for Individualizing Medicine’s Microbiome Project.

Results

Whereas injection of the anti-PD-L1 antibody (clone 10B5) controlled tumor growth compared to treatment with an isotype control in SPF female mice with B16-OVA (p = 0.05), PD-L1 blockade had no effect on tumor growth in female axenic mice with B16-OVA (p = 0.20) or male axenic mice with B16-OVA (p = 0.34) or axenic mice with LLC (p = 0.56).

Conclusions

PD-L1 blockade therapy loses its anti-tumor efficacy in axenic mice. The microbiome may influence the efficacy of PD-L1 blockade through of its effects on both innate and adaptive immune responses to tumors.

Clinical trial identification

Legal entity responsible for the study

Aaron Mansfield at Mayo Clinic

Funding

National Institutes of Health; Mayo Clinic's Center for Individualizing Medicine Microbiome Project

Disclosure

All authors have declared no conflicts of interest.