Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer  

作　　者：Tong Shen Jing-Lin Liu Chu-Yi Wang Youlutuziayi Rixiati Shi Li Ling-Dong Cai Yuan-Yuan Zhao Jian-Ming Li 

机构地区：[1]Department of Pathology,Soochow University Medical School,Suzhou,China [2]Department of Pathology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第4期1302-1319,共18页信号转导与靶向治疗（英文）

基　　金：This work was supported by National Key R&D Program of China(2019YFA0802400);National Natural Science Foundation of China(81525020 and U1801282);the Guangzhou Science and Technology Plan Projects(Health Medical Collaborative Innovation Program of Guangzhou)(201803040019);This work was also supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

摘　　要：The mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear.Here,using clinical samples from lung metastases of CRC patients,we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC.Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin,one member of the leucine-rich repeat and PDZ domain(LAP)family,was involved in the lung metastases.Erbin deletion in B cells suppressed lung metastasis of CRC in vivo.And,deletion of Erbin in B cells enhanced the killing effects of CD8+T cells on tumor cells.Mechanistically,Erbin knockout attenuated TGFp-mediated suppression of migration of CXCR5+lgA+cells and STAT6-mediated PD1 expression.Our study uncovered a key role of Erbin in regulating PD1+lgA+B cells in lung metastasis of CRC.Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice,suggesting the potential option for treatment of lung metastasis of CRC.

关 键 词：PD1 METASTASIS LUNG 

分 类 号：R734.2[医药卫生—肿瘤]