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小鼠模型肿瘤植入部位对抗 PD-1 免疫检查点治疗获得性耐药的影响。

Impact of mouse model tumor implantation site on acquired resistance to anti-PD-1 immune checkpoint therapy.

机构信息

Univ Lyon, Université Claude Bernard Lyon, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.

R&D Department, Antineo, Lyon, France.

出版信息

Front Immunol. 2023 Jan 10;13:1011943. doi: 10.3389/fimmu.2022.1011943. eCollection 2022.

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.

摘要

简介

使用肿瘤皮下(SC)植入而不是原位部位可能会引起重大偏差,特别是在免疫治疗领域。

方法

在这项研究中,我们开发并表征了 MC38 模型,这些模型被皮下和原位植入,对抗 PD1 治疗敏感或耐药。我们通过流式细胞术在基线和治疗后对肿瘤免疫浸润进行了表征。

结果与讨论

我们的结果表明,在基础状态下,SC 和原位模型之间存在多种差异,这些差异在治疗后趋于相似。这些结果强调了在使用免疫治疗药物进行临床前研究时,需要考虑肿瘤植入部位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bcd/9872099/78196926da15/fimmu-13-1011943-g001.jpg

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