Hematopathology Division and Department of Pathology, Duke University Medical Center, Durham, NC, United States.
Duke University Cancer Institute, Durham, NC, United States.
Front Immunol. 2024 Jan 29;15:1335689. doi: 10.3389/fimmu.2024.1335689. eCollection 2024.
Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.
We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.
We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patients with low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response.
TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication.
我们之前的研究表明,弥漫性大 B 细胞淋巴瘤(DLBCL)中的肿瘤浸润淋巴细胞(TIL),包括正常 B 细胞、T 细胞和自然杀伤(NK)细胞,对接受标准化疗免疫治疗的患者的临床结局有显著的积极影响。在这项研究中,为了全面了解肿瘤免疫微环境(TIME),我们在杜克大学医学中心收集了 102 例诊断为 DLBCL 的患者的流式细胞术队列。
我们收集了诊断性流式细胞术数据,包括患者在临床就诊时新鲜活检组织中 T 细胞、异常 B 细胞、正常 B 细胞、浆细胞、NK 细胞、单核细胞和粒细胞的比例,并分析了与患者生存的相关性以及不同细胞群之间的相关性。
我们发现,所有活细胞中 T 细胞比例低,T 细胞与异常 B 细胞的比例低与生存显著较差相关,而总 B 细胞中正常 B 细胞比例高(或正常 B 细胞与异常 B 细胞的比例高)和所有活细胞中 NK 细胞比例高与 DLBCL 患者的生存显著改善相关。排除少数 T 细胞比例低的患者后,所有 B 细胞中的正常 B 细胞比例,但不是所有细胞中的 T 细胞比例,继续显示出显著的预后效果。数据显示 T 细胞与正常 B 细胞之间以及粒细胞与单核细胞之间存在显著的正相关关系。此外,我们基于临床和流式细胞术因素构建了一个预后模型,该模型将 DLBCL 队列分为两组,两组患者的生存和治疗反应差异显著。
TIL,包括正常 B 细胞、T 细胞和 NK 细胞,与 DLBCL 的良好临床结局相关,能够定量评估 TIME 的流式细胞术可能具有额外的预后临床效用。