The effects of tumor cell heterogeneity on radiotherapy

• 1、Cyrus Tang Hematology Center, Soochow University,Suzhou 215123

Abstract：Tumor cell heterogeneity is a crucial factor contributing to cancer treatment resistance. Although its resistance mechanisms in oncogen targeted therapy have been extensively investigated, how tumor cell heterogeneity affects on the efficacy of radiotherapy remains largely unknown.The tumors derived from single-cell clones (SCCs) isolated from mouse EO771 breast tumor cell lines were treated with radiotherapy. The responses of various SCC breast tumor models to radiotherapy were heterogeneous, which were classified as radiotherapy-sensitive and radiotherapy-resistant types based on the values of tumor growth inhibition. Tumor models derived from mixing the same type of SCCs exhibited similar radiotherapy sensitivity to the premixing SCC tumor models, but tumor models derived from mixing different types of SCCs were resistant to radiotherapy, which was similar to the premixing radiotherapy-resistant SCC tumor models. Radiotherapy did not show consistent and significant impacts on the proportions of CD8+ T cells, tumor vessel density, and vascular perfusion in these tumor models. However, before radiotherapy, vascular perfusion in the radiotherapy-sensitive tumor models of various SCCs and their combinations was significantly higher than that of radiotherapy-resistant tumor models. These results suggest that the impacts of tumor cell heterogeneity on radiotherapy sensitivity are determined by the characteristics of tumor cell clones, but not the quantity of tumor cell clones. Among them, radiotherapy-resistant clones exert a predominant influence, potentially through the reduction of tumor vessel perfusion.

Keywords： Oncology Tumor cell heterogeneity Radiotherapy sensitivity Tumor microenvironment