Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer  

作　　者：Shan Long Yibing Zhao Yuanyuan Xu Bo Wang Haixia Qiu Hongyou Zhao Jing Zeng Defu Chen Hui Li Jiakang Shao Xiaosong Li Ying Gu 

机构地区：[1]School of Medicine,Nankai University Tianjin,300072,P.R.China [2]Department of Laser Medicine The First Medical Center of Chinese PLA General Hospital Beijing 100853,P.R.China [3]Department of Oncology The Seventh Medical Center of Chinese PLA General Hospital Beijing 100039,P.R.China [4]School of Basic Medicine,Guizhou Medical University Guiyang 550025,Guizhou,P.R.China [5]College of Medical Technology,Beijing Institute of Technology Beijing 100081,P.R.China [6]Medical School of Chinese PLA Beijing 100853,P.R.China

出　　处：《Journal of Innovative Optical Health Sciences》2024年第1期87-103,共17页创新光学健康科学杂志（英文）

基　　金：supported by the National Key Research and Development Program of China[2018YFB0407200];National Natural Science Foundation of China[61975239];Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences[2019-I2M-5061].

摘　　要：Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

关 键 词：Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor im-mune effects metastatic breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]