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2021, Signal Transduct Target Ther .. DOI: 10.1038/s41392-021-00501-x PMID: 33707428 PMCID: PMC7952714
Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer
Tong Shen, Jing-Lin Liu, Chu-Yi Wang, Youlutuziayi Rixiati, Shi Li, Ling-Dong Cai, Yuan-Yuan Zhao, Jian-Ming Li
Abstract:
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 TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression. Our study uncovered a key role of Erbin in regulating PD1+ IgA+ 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.
2022-05-31 22:51:00
#paper  DOI: 10.1038/s41392-021-00501-x Signal Transduct Target Ther. 2021. Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer. 结直肠癌是全球致死率最高的癌症之一,其中肺是结直肠癌转移的第二大器官,但目前关于结直肠癌肺转移的机制以及涉及到的肿瘤环境中的关键因子还尚不明确。本文作者发现结直肠癌肺转移中lgA产生的肠道免疫网络明显失调。单细胞RNA测序发现Erbin(富含亮氨酸重复序列和PDZ域(LAP)家族的一员)阳性的B细胞亚型参与了肺转移。敲除B细胞的Erbin抑制体内结直肠癌的肺转移。从机制上讲,Erbin基因敲除减弱了TGFβ介导的CXCR5 + IgA +细胞迁移和STAT6介导的PD1表达的抑制。该研究揭示了Erbin在CRC肺转移中调节PD1 + IgA + B细胞的关键作用。靶向Erbin以及联合使用中和B细胞和中和PD1的抗体可抑制小鼠结直肠癌的肺转移,该研究为治疗结直肠癌肺转移提供潜在的选择。
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