The recurrence rate of lymphoma is very high, and tumor stem cells may be an important mechanism. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can inhibit antitumor immunity and promote cancer progression, but its role and mechanism in lymphoma are still unclear. Here we collected lymphoma tissue and peripheral blood from patients with diffuse large B-cell lymphoma (DLBCL). Results showed that CTLA-4 expression and CD44+ cell in the high-risk group were significantly higher than that in the low-risk group. Correlation analysis showed that CTLA-4 expression positively correlated with CD44+ cell in lymphoma tissue and regulatory T (Treg) cells in lymphocytes. In vitro experiment showed that CTLA-4 increased the ratio of lymphoma stem cells, and proliferation and invasion of lymphoma cells through TGF-β pathway. Moreover, CTLA-4 enhanced the proliferation of Treg cells induced by lymphoma cells. Animal experiments showed that CTLA-4 can promote transplanted lymphoma growth. Immunohistochemistry results showed that both Ki-67 and CD44+ cells increased significantly in the CTLA-4 group. TGF-β neutralization can significantly block these effects of CTLA-4. In conclusion, CTLA-4 promoted DLBCL progression through lymphoma stem cell enrichment and immunosuppression.

中文翻译：

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CTLA-4通过肿瘤干细胞富集和免疫抑制促进淋巴瘤进展

淋巴瘤的复发率非常高，肿瘤干细胞可能是一个重要机制。细胞毒T淋巴细胞相关抗原4（CTLA-4）可抑制抗肿瘤免疫，促进癌症进展，但其在淋巴瘤中的作用和机制尚不清楚。在这里，我们收集了弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者的淋巴瘤组织和外周血。结果显示，高危组CTLA-4表达和CD44+细胞明显高于低危组。相关性分析显示CTLA-4表达与淋巴瘤组织中的CD44+细胞和淋巴细胞中的调节性T（Treg）细胞呈正相关。体外实验表明，CTLA-4通过TGF-β通路提高淋巴瘤干细胞的比例，提高淋巴瘤细胞的增殖和侵袭能力。此外，CTLA-4 增强了淋巴瘤细胞诱导的 Treg 细胞的增殖。动物实验表明CTLA-4可以促进移植淋巴瘤的生长。免疫组织化学结果显示，CTLA-4 组的 Ki-67 和 CD44+ 细胞均显着增加。TGF-β中和可以显着阻断CTLA-4的这些作用。总之，CTLA-4 通过淋巴瘤干细胞富集和免疫抑制促进 DLBCL 进展。