The combination of high-dose radiotherapy and low-dose radiotherapy patterns can enhance antitumor immunity in non-small cell lung cancer

Abstract

Abstract Purpose The function of HDRT in promoting antitumor immunity has both positive and negative effects, whereas LDRT appears to play an essential role in controlling the tumor immune microenvironment. New preclinical evidence indicates that the combination of HDRT and LDRT in radiotherapy protocols offers the benefits of both.Hence, we examined the impact and process of utilizing immunotherapy in conjunction with HDRT and LDRT radiation to combat tumor immunity. Methods and Materials: The optimal low-dose irradiation was selected by analyzing the RNA sequence transcriptome and immunohistochemistry using a model of bilateral mouse tumor irradiation.Following the addition of ICI, the presence of immune cells within the tumor was identified through the use of immunohistochemistry (IHC) and flow cytometry (FCM).Subsequently, the possible means of improving the immune response against tumors was explored through bioinformatics analysis and experimental verification. Results Administering HDRT (20 Gy) to the primary tumor along with LDRT (6 Gy) to the abscopal tumor resulted in an improved abscopal response in comparison to solely administering HDRT treatment.The combination of HDRT, LDRT, and ICI can increase the effectiveness of ICI treatment.According to the IHC and FCM findings, the presence of immune cells in the triple therapy group was notably higher.The improvement of the abscopal impact was primarily linked to the increase in the chemokine CCL17 and the infiltration of CD8 + T-cells triggered by CCL17. Conclusions Our research revealed that the application of HDRT/LDRT radiation together could enhance the immune cell infiltration in mice tumors and boost the effectiveness of immunotherapy.