%0 Journal Article
%T oHSV2-mGM repolarizes TAMs and cooperates with αPD1 to reprogram the immune microenvironment of residual cancer after radiofrequency ablation.
%A Zhu L
%A Huang J
%A Zhang S
%A Cai Q
%A Guo X
%A Liu B
%A Chen L
%A Zheng C
%J Biomed Pharmacother
%V 178
%N 0
%D 2024 Sep 24
%M 39053421
%F 7.419
%R 10.1016/j.biopha.2024.117060
%X <B>BACKGROUND: </B>Due to the size and location of the tumor, incomplete radiofrequency ablation (iRFA) of the target tumor inhibits tumor immunity. In this study, a murine herpes simplex virus (oHSV2-mGM) armed with granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed to explore its effect on innate and adaptive immunity during iRFA, and the inhibitory effect of programmed cell death-1 (PD1) on tumor.<BR><B>METHODS: </B>We verified the polarization and activation of RAW264.7 cells mediated by oHSV2-mGM in vitro. Subsequently, we evaluated the efficacy of oHSV2-mGM alone and in combination with αPD1 in the treatment of residual tumors after iRFA in two mouse models. RNA-seq was used to characterize the changes of tumor microenvironment.<BR><B>RESULTS: </B>oHSV2-mGM lysate effectively stimulated RAW264.7 cells to polarize into M1 cells and activated M1 phenotypic function. In the macrophage clearance experiment, oHSV2-mGM activated the immune response of tumor in mice. The results in vivo showed that oHSV2-mGM showed better anti-tumor effect in several mouse tumor models. Finally, oHSV2-mGM combined with PD1 antibody can further enhance the anti-tumor effect of oHSV2-mGM and improve the complete remission rate of tumor in mice.<BR><B>CONCLUSIONS: </B>The application of oHSV2-mGM leads to the profound remodeling of the immune microenvironment of residual tumors. oHSV2-mGM also works in synergy with PD1 antibody to achieve complete remission of tumors that do not respond well to monotherapy at immune checkpoints. Our results support the feasibility of recombinant oncolytic virus in the treatment of residual tumors after iRFA, and propose a new strategy for oncolytic virus treatment of tumors.