AUTHOR=Denis Morgane , Mathé Doriane , Micoud Manon , Choffour Pierre-Antoine , Grasselly Chloé , Matera Eva-Laure , Dumontet Charles TITLE=Impact of mouse model tumor implantation site on acquired resistance to anti-PD-1 immune checkpoint therapy JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1011943 DOI=10.3389/fimmu.2022.1011943 ISSN=1664-3224 ABSTRACT=Introduction

The use of tumor subcutaneous (SC) implantations rather than orthotopic sites is likely to induce a significant bias, in particular, in the field of immunotherapy.

Methods

In this study, we developed and characterized MC38 models, implanted subcutaneously and orthotopically, which were either sensitive or rendered resistant to anti-PD1 therapy. We characterized the tumor immune infiltrate by flow cytometry at baseline and after treatment.

Results and Discussion

Our results demonstrate several differences between SC and orthotopic models at basal state, which tend to become similar after therapy. These results emphasize the need to take into account tumor implantation sites when performing preclinical studies with immunotherapeutic agents.