Department of Hematology, Nanfang Hospital, Southern medical University, Guangzhou 510515, China.
Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Int Immunopharmacol. 2017 Sep;50:146-151. doi: 10.1016/j.intimp.2017.06.020. Epub 2017 Jun 26.
Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive subtype of non-Hodgkin's lymphomas, with limited treatment options in refractory and relapsed patients. Growing evidence supports the notion that CD8 T cell immunity could be utilized to eliminate B cell lymphomas. CXCR5CD8 T cell is a novel cell subtype and share CXCR5 expression with CD19 tumor cells. In this study, we investigated the frequency and function of existing CXCR5CD8 T cells in DLBCL patients. We found that DLBCL patients as a group demonstrated significantly higher level of CXCR5CD8 T cells than healthy individuals, with huge variability in each patient. Using anti-CD3/CD28-stimulated CD8 T cells as effector (E) cells and autologous CD19 tumor cells as target (T) cells, at high E:T ratio, no difference between the intensities of CXCR5CD8 T cell- and CXCR5CD8 T cell-mediated cytotoxicity were observed. However, at intermediate and low E:T ratios, the CXCR5CD8 T cells presented stronger cytotoxicity than CXCR5CD8 T cells. The expressions of granzyme A, granzyme B, and perforin were significantly higher in CXCR5CD8 T cells than in CXCR5CD8 T cells, with no significant difference in the level of degranulation. Tumor cells in DLBCL were known to secrete high level of interleukin 10 (IL-10). We therefore blocked the IL-10/IL-10R pathway, and found that the expressions of granzyme A, granzyme B, and perforin by CXCR5CD8 T cells were significantly elevated. Together, these results suggest that CXCR5CD8 T cells are potential candidates of CD8 T cell-based immunotherapies, could mediate elimination of autologous tumor cells in DLBCL patients, but are also susceptible to IL-10-mediated suppression.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种常见且侵袭性较强的非霍奇金淋巴瘤亚型，对于难治性和复发性患者的治疗选择有限。越来越多的证据支持这样一种观点，即 CD8 T 细胞免疫可以用于消除 B 细胞淋巴瘤。CXCR5CD8 T 细胞是一种新型细胞亚群，与 CD19 肿瘤细胞共享 CXCR5 表达。在这项研究中，我们研究了 DLBCL 患者中现有 CXCR5CD8 T 细胞的频率和功能。我们发现，DLBCL 患者作为一个群体，与健康个体相比，CXCR5CD8 T 细胞水平显著升高，且每个患者之间存在巨大差异。使用抗 CD3/CD28 刺激的 CD8 T 细胞作为效应（E）细胞，自体 CD19 肿瘤细胞作为靶（T）细胞，在高 E:T 比下，CXCR5CD8 T 细胞和 CXCR5CD8 T 细胞介导的细胞毒性强度没有差异。然而，在中低 E:T 比下，CXCR5CD8 T 细胞表现出比 CXCR5CD8 T 细胞更强的细胞毒性。CXCR5CD8 T 细胞中的颗粒酶 A、颗粒酶 B 和穿孔素表达明显高于 CXCR5CD8 T 细胞，脱颗粒水平无显著差异。已知 DLBCL 中的肿瘤细胞会分泌高水平的白细胞介素 10（IL-10）。因此，我们阻断了 IL-10/IL-10R 途径，发现 CXCR5CD8 T 细胞中的颗粒酶 A、颗粒酶 B 和穿孔素表达显著升高。总之，这些结果表明，CXCR5CD8 T 细胞是基于 CD8 T 细胞免疫疗法的潜在候选者，能够介导 DLBCL 患者自体肿瘤细胞的消除，但也容易受到 IL-10 介导的抑制。
