Abstract
Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer. Here, we developed a hybrid nanovesicle to stratify radiotherapy response by activatable inflammation magnetic resonance imaging (aiMRI) approach. The high Pearson’s correlation coefficient R values are obtained from the correlations between the T1 relaxation time changes at 24–48 h and the ensuing adaptive immunity (R = 0.9831) at day 5 and the tumor inhibition ratios (R = 0.9308) at day 18 after different treatments, respectively. These results underscore the role of acute inflammatory oxidative response in bridging the innate and adaptive immunity in tumor radiotherapy. Furthermore, the aiMRI approach provides a non-invasive imaging strategy for early prediction of the therapeutic outcomes in cancer radiotherapy, which may contribute to the future of precision medicine in terms of prognostic stratification and therapeutic planning.
Highlights
Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer
The segregation of immature (CD101−) and mature (CD101+) neutrophil subsets revealed that mouse tumors treated with X-ray + G-CSF are responsible for a significantly higher fraction of mature neutrophils in the tumor, but not in the blood, when compared with the other groups (X-ray or G-CSF alone) (Supplementary Fig. 31). These results further indicate that RTmediated neutrophil infiltration can contribute to the oxidative stress in tumor cells, which could be alternatively quantified by the activatable inflammation magnetic resonance imaging (aiMRI)
The results indicated that the Nox-deficient mice had significantly lower rate of inflammatory response derived from the aiMRI experiments, which correlated well with the lower tumor inhibition rate either with or without G-CSF treatment at late time (Pearson’s R = 0.9007)
Summary
Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer. The high Pearson’s correlation coefficient R values are obtained from the correlations between the T1 relaxation time changes at 24–48 h and the ensuing adaptive immunity (R = 0.9831) at day 5 and the tumor inhibition ratios (R = 0.9308) at day 18 after different treatments, respectively. These results underscore the role of acute inflammatory oxidative response in bridging the innate and adaptive immunity in tumor radiotherapy. Therapy-induced inflammatory responses are responsible to the adaptive immune responses through ROS-mediated cell apoptosis and the ensuing activation of immune T cells[24], in which neutrophils may play an important role in bridging the innate and adaptive immunity
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