Depth of tumor implantation affects response to in situ vaccination in a syngeneic murine melanoma model

作者：Peter M. Carlson, Manasi Mohan, Matthew Rodriguez, Владимир Субботин, Claire Sun, Ravi B. Patel, Jen Birstler, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Zachary S. Morris, Amy K. Erbe, Paul M. Sondel · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2020-002107 · 被引用次数：23 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers

An important component of research using animal models is ensuring rigor and reproducibility. This study was prompted after two experimenters performing virtually identical studies obtained different results when syngeneic B78 murine melanoma cells were implanted into the skin overlying the flank and treated with an in situ vaccine (ISV) immunotherapy. Although both experimenters thought they were using identical technique, we determined that one was implanting the tumors intradermally (ID) and the other was implanting them subcutaneously (SC). Though the baseline in vivo immunogenicity of tumors can depend on depth of their implantation, the response to immunotherapy as a function of tumor depth, particularly in immunologically ‘cold’ tumors, has not been well studied. The goal of this study was to evaluate the difference in growth kinetics and response to immunotherapy between identically sized melanoma tumors following ID versus SC implantation. We injected C57BL/6 mice with syngeneic B78 melanoma cells either ID or SC in the flank. When tumors reached 190–230 mm 3 , they were grouped into a ‘wave’ and treated with our previously published ISV regimen (12 Gy local external beam radiation and intratumoral hu14.18-IL2 immunocytokine). Physical examination demonstrated that ID-implanted tumors were mobile on palpation, while SC-implanted tumors became fixed to the underlying fascia. Histologic examination identified a critical fascial layer, the panniculus carnosus, which sep...