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Supplementary Data from Claudin-12 Deficiency Inhibits Tumor Growth by Impairing Transendothelial Migration of Myeloid-Derived Suppressor Cells

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posted on 2023-03-31, 05:24 authored by Hong Cao, Chen Ni, Le Han, Ruoqi Wang, Rosel Blasig, Reiner Haseloff, Yue Qin, Jie Lan, Xiaohan Lou, Pan Ma, Xiaohan Yao, Linlin Wang, Fei Wang, Linyu Zhu, Ningjing Lei, Ingolf E. Blasig, Zhihai Qin
Supplementary Data from Claudin-12 Deficiency Inhibits Tumor Growth by Impairing Transendothelial Migration of Myeloid-Derived Suppressor Cells

Funding

National Science and Technology Major Project

National Natural Science Foundation of China

Key Project of Medical Science and Technology of Henan Province

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ARTICLE ABSTRACT

Migration of myeloid-derived suppressor cells (MDSC) out of the circulation, across vascular walls, and into tumor is crucial for their immunosuppressive activity. A deeper understanding of critical junctional molecules and the regulatory mechanisms that mediate the extravasation of MDSCs could identify approaches to overcome cancer immunosuppression. In this study, we used mice deficient in tight junction protein Claudin-12 (Cldn12) compared with wild-type mice and found that loss of host Cldn12 inhibited the growth of transplanted tumors, reduced intratumoral accumulation of MDSCs, increased antitumor immune responses, and decreased tumor vascular density. Further studies revealed that Cldn12 expression on the cell surface of both MDSCs and endothelial cells (EC) is required for MDSCs transit across tumor vascular ECs. Importantly, expression of Cldn12 in MDSCs was modulated by GM-CSF in an AKT-dependent manner. Therefore, our results indicate that Cldn12 could serve as a promising target for restoring the antitumor response by interfering with MDSCs transendothelial migration. Claudin-12–mediated homotypic interactions are critical for migration of myeloid-derived suppressor cells across vascular walls into tumor tissue, providing a potential therapeutic approach to overcome cancer immunosuppression.

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