A MR/PA Dual-Modality Imaging for quantitative evaluation of tumor vascular and immune microenvironment

Abstract

Backgroud: Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and there are few reports on multimodal imaging markers in the study of tumor therapeutic response. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance imaging /photoacoustic imaging (MR/PA) imaging, and to explore the therapeutic effect of tumor radiotherapy combined with PD-L1 immunocheckpoint inhibitor. Methods The tumor-bearing mice (TBM) were randomly allocated to six groups: the low-dose group, high-dose group, low-dose + PD-L1 group, high-dose + PD-L1 group, anti-PD-L1 group and control group. Animals received 2 Gy/14 Fx (low-dose group) or 8 Gy/3 Fx (high-dose group) radiation and the combination treatment groups were given an anti-PD-L1 antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of breast cancer model to different doses of radiotherapy, combined with histopathological techniques to observe the changes of tumor vessels and microenvironment. Results The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity (SI) decreased significantly (p༜0.05). Compared with those in the other groups, the tumor vascular density decreased significantly, and the vascular maturity index (VMI) increased significantly in the low-dose group (p༜0.05). The PA images showed that the deoxyhemoglobin (HbR) and total hemoglobin (HbT) levels decreased and the SO2 level increased after radiation treatment. In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) and natural killer (NK) cells and increased PD-L1 expression in the tumors (p༜0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice, and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (p = 0. 002). Conclusion Differential fractionation radiotherapy doses exert different effects on tumor vascular remodeling and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which is of great significance for the clinical applications of radiotherapy combined with immunotherapy.