TLR1/TLR2 signaling blocks the suppression of monocytic myeloid-derived suppressor cell by promoting its differentiation into M1-type macrophage.


Biotherapy Research Center, Fudan University, Shanghai, 200032, China; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: [Email]


Myeloid derived suppressor cells (MDSCs) play a key role in tumor immunosuppressive microenvironment, which helps tumors avoid immune destruction. Blocking the suppressive activities of MDSCs could be a promising strategy to enhance the effect of anti-tumor immunotherapies. In this study, we found that TLR1/TLR2 expression predicted favorable prognosis of lung cancer patients. In the related mice tumor model, TLR1/TLR2 activation by synthetic bacterial lipoprotein (BLP), a TLR1/2 agonist, greatly inhibited tumor growth and selectively decreased monocytic MDSCs (M-MDSCs). Furthermore, BLP treatment redirected M-MDSC differentiation towards M1 macrophage through JNK pathway, and thus blocked the suppressive activity of M-MDSCs in a TLR2-dependent manner. Therefore, our data demonstrated that TLR2 could be a promising biomarker and a potential immunotherapeutic target for lung cancer.


BLP,M-MDSC,M1 macrophage,TLR1/TLR2,