Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1
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RESEARCH
Open Access
Small-molecule MMP2/MMP9 inhibitor SB3CT modulates tumor immune surveillance by regulating PD-L1 Youqiong Ye1,2,3*†, Xinwei Kuang1,4,5,6†, Zuozhong Xie1,4,5,6†, Long Liang1,7, Zhao Zhang3, Yongchang Zhang8, Fangyu Ma9, Qian Gao1,4,5,6, Ruimin Chang1,4,5,6, Heng-Huan Lee10, Shuang Zhao1,4,5,6, Juan Su1,4,5,6, Hui Li7, Jingbo Peng11, Huifang Chen2, Minzhu Yin1,4,5,6, Cong Peng1,4,5,6, Nong Yang8, Jing Wang12, Jing Liu7, Hong Liu1,4,5,6,13*, Leng Han3* and Xiang Chen1,4,5,6*
Abstract Background: Immune checkpoint blockade (ICB) therapy has demonstrated considerable clinical benefit in several malignancies, but has shown favorable response in only a small proportion of cancer patients. Recent studies have shown that matrix metalloproteinases (MMPs) are highly associated with the microenvironment of tumors and immune cells. However, it is unknown whether MMPs are involved in immunotherapy. Methods: Here, we used integrative analysis to explore the expression landscape of the MMP family and its association with immune features across multiple cancer types. We used T cell cytotoxicity-mediated tumor killing assay to determine the co-cultured T cell activity of SB-3CT, an MMP2/9 inhibitor. We then used in vitro assays to examine the regulating roles of SB-3CT on PD-L1. We further characterized the efficacy of SB-3CT, in combination with anti-PD-1 and/or anti-CTLA4 treatment in mouse models with melanoma and lung cancer. (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected]; [email protected] † Youqiong Ye, Xinwei Kuang and Zuozhong Xie contributed equally to this work. 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China 3 Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA Full list of author information is available at the end of the article
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