Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Rep. 2019 Feb 19;26(8):2178-2193.e3. doi: 10.1016/j.celrep.2019.01.085.
Follicular lymphoma (FL) is an indolent B cell malignancy characterized by an extensive but poorly functional T cell infiltrate in the tumor microenvironment. Using mass cytometry, we identified at least 12 subsets of intratumoral CD4 T cells, 3 of which were unique to FL biopsies versus control tissues. Of these subsets, the frequency of naive T cells correlated with improved patient survival. Although total PD-1 T cell numbers were not associated with patient outcome, specific PD-1 T cell subpopulations were associated with poor survival. Intratumoral T cells lacking CD27 and CD28 co-stimulatory receptor expression were enriched in FL and correlated with inferior patient outcomes. In vitro models revealed that CD70 lymphoma cells played an important role in expanding this population. Taken together, our mass cytometry results identified CD4 memory T cell populations that are poorly functional due to loss of co-stimulatory receptor expression and are associated with an inferior survival in FL.
滤泡性淋巴瘤（FL）是一种惰性 B 细胞恶性肿瘤，其肿瘤微环境中存在广泛但功能较差的 T 细胞浸润。使用质谱流式细胞术，我们鉴定了至少 12 种肿瘤内 CD4 T 细胞亚群，其中 3 种仅存在于 FL 活检组织中，而不存在于对照组织中。在这些亚群中，幼稚 T 细胞的频率与患者生存改善相关。虽然总 PD-1 T 细胞数量与患者预后无关，但特定的 PD-1 T 细胞亚群与不良预后相关。缺乏 CD27 和 CD28 共刺激受体表达的肿瘤内 T 细胞在 FL 中富集，并与患者预后不良相关。体外模型表明，CD70 淋巴瘤细胞在扩增该细胞群中发挥了重要作用。综上所述，我们的质谱流式细胞术结果鉴定了由于共刺激受体表达缺失而功能较差的 CD4 记忆 T 细胞群体，与 FL 患者的不良生存相关。
