Yang Fafen, Zhao Jingjie, Luo Xiuzhuang, Li Tong, Wang Zechen, Wei Qiuju, Lu Heming, Meng Yiliang, Cai Kai, Lu Liuying, Lu Yushi, Chen Lifen, Sooranna Suren Rao, Luo Linxue, Song Jian, Meng Lingzhang
Center for Systemic Inflammation Research (CSIR), School of Preclinical Medicine, Youjiang Medical University for Nationalities, Baise, China.
Department of Renal Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Front Oncol. 2021 Aug 12;11:731896. doi: 10.3389/fonc.2021.731896. eCollection 2021.
Although immune therapy can improve the treatment of clear cell renal cell carcinoma (ccRCC) significantly, there are still a large proportion of ccRCC patients who progress to metastasis. Targeting the pro-metastatic immune cell in the ccRCC microenvironment could provide a solution to this problem. In this study, B cells in ccRCC biopsies were identified by using scRNA-seq and flow cytometry. The findings indicated the presence of a pro-metastatic B cell type which could be further classified into 3 subpopulations, MARCH3, B2M and DTWD1, based on their large-scaled genetic profiles, rather than traditional Immature/Mature ones. Although all of the 3 subpopulations appeared to contribute to distant metastasis, B cell (B2M) was deemed to be the most essential. Moreover, STX16, CLASRP, ATIC, ACIN1 and SEMA4B, were genes found to be commonly up-regulated in the 3 subpopulations and this was correlated to a poor prognosis of ccRCC. Furthermore, the heterogeneity of plasma cells in ccRCC was also found to contribute to metastasis of the disease. This study offers potential novel therapeutic targets against distant metastasis of cancers, and can help to improve the therapeutic efficiency of ccRCC patients.
尽管免疫疗法能显著改善肾透明细胞癌（ccRCC）的治疗效果，但仍有很大比例的ccRCC患者会进展为转移。靶向ccRCC微环境中促转移的免疫细胞可能为解决这一问题提供办法。在本研究中，通过使用单细胞RNA测序（scRNA-seq）和流式细胞术鉴定了ccRCC活检组织中的B细胞。研究结果表明存在一种促转移的B细胞类型，根据其大规模基因图谱，而非传统的未成熟/成熟类型，可进一步分为3个亚群，即MARCH3、B2M和DTWD1。尽管这3个亚群似乎都对远处转移有作用，但B细胞（B2M）被认为是最关键的。此外，发现STX16、CLASRP、ATIC、ACIN1和SEMA4B在这3个亚群中普遍上调，且这与ccRCC的不良预后相关。此外，还发现ccRCC中浆细胞的异质性也有助于该疾病的转移。本研究提供了针对癌症远处转移的潜在新型治疗靶点，并有助于提高ccRCC患者的治疗效果。
