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

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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… Click to show full abstract

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.

Keywords: tlr1 tlr2; myeloid derived; derived suppressor; tlr2

Journal Title: Molecular immunology
Year Published: 2019

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