Mao Hui, Pan Fei, Wu Zhiyong, Wang Zhikuan, Zhou Yanhua, Zhang Pengfei, Gou Miaomiao, Dai Guanghai
Department of Oncology, Chinese PLA General Hospital, Beijing, China.
Department of Gastroenterology, Chinese PLA General Hospital, Beijing, China.
Int Immunopharmacol. 2017 Aug;49:95-101. doi: 10.1016/j.intimp.2017.05.018. Epub 2017 May 27.
Inflammation plays a critical role in the initiation of colorectal cancer but is also required to mediate antitumor immunity in established tumors. Therefore, identifying the cellular and molecular components in colorectal tumors is necessary for the understanding of tumor progression and the development of novel treatment strategies. In this study, we demonstrated that a specific subtype of regulatory B cells, the CD19CD27 plasmablasts, was enriched in the colorectal tumor microenvironment. This CD19CD27 plasmablast subset presented high interleukin 10 (IL-10) expression but not transforming growth factor-β (TGF-β) secretion. Phenotypically, the tumor-infiltrating IL-10 CD19CD27 plasmablasts presented lower CD24, CD38, and IgA, and higher Tim-1 and IgG expression compared to the IL-10 CD19CD27 plasmablasts. The tumor-infiltrating IL-10 CD19CD27 plasmablasts were found to be gut-homing due to their higher expression of α4β7 while peripheral blood B cells did not show the same characteristic. When cocultured with autologous T cells, CD19CD27 plasmablasts demonstrated potent activity in suppressing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) expression but did not promote Foxp3 expression. Overall, this study demonstrate that in colorectal cancer, CD19CD27 plasmablasts make up a large percentage in tumor-infiltrating lymphocytes and possess potent immunoregulatory functions, and thus could be utilized in future therapeutic strategies.
炎症在结直肠癌的起始过程中起着关键作用，但在已形成的肿瘤中介导抗肿瘤免疫也需要炎症。因此，确定结直肠癌肿瘤中的细胞和分子成分对于理解肿瘤进展和开发新的治疗策略是必要的。在本研究中，我们证明了一种特定亚型的调节性B细胞，即CD19CD27浆母细胞，在结直肠癌肿瘤微环境中富集。该CD19CD27浆母细胞亚群呈现高白细胞介素10（IL-10）表达，但不分泌转化生长因子-β（TGF-β）。从表型上看，与IL-10 CD19CD27浆母细胞相比，肿瘤浸润性IL-10 CD19CD27浆母细胞呈现较低的CD24、CD38和IgA表达，以及较高的Tim-1和IgG表达。由于肿瘤浸润性IL-10 CD19CD27浆母细胞较高的α4β7表达，发现它们具有归巢至肠道的特性，而外周血B细胞则不具有相同特征。当与自体T细胞共培养时，CD19CD27浆母细胞在抑制干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）表达方面表现出强大活性，但不促进Foxp3表达。总体而言，本研究表明，在结直肠癌中，CD19CD27浆母细胞在肿瘤浸润淋巴细胞中占很大比例，并具有强大的免疫调节功能，因此可用于未来的治疗策略。
