肿瘤细胞治疗研究
英文原题：Spatial Profiling and Prognostic Role of Tumor-Infiltrating CD8+ T and CD20+ B Cells in Metastatic Clear Cell Renal Cell Carcinoma Treated with Sequential Tyrosine Kinase Inhibitors and Nivolumab.
Spatial Profiling and Prognostic Role of Tumor-Infiltrating CD8+ T and CD20+ B Cells in Metastatic Clear Cell Renal Cell Carcinoma Treated with Sequential Tyrosine Kinase Inhibitors and Nivolumab.
我们的研究结果表明，肿瘤浸润性CD20+ B细胞的空间定位和密度是TKIs治疗中PFS不良的潜在预测因素，而肿瘤周围区域较高的CD8+ T细胞浸润可能是nivolumab治疗中PFS延长的潜在预测因素。
背景：已知TIL（肿瘤浸润淋巴细胞）（TILs）影响透明细胞肾细胞癌的疾病进展和治疗反应。本研究旨在评估在接受酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂nivolumab序贯治疗的转移性透明细胞肾细胞癌（mRCC-cc）患者中，T细胞和B细胞浸润模式的预后和预测相关性。 方法：在这项回顾性队列研究中，通过免疫组织化学分析免疫细胞密度（CD3+、CD8+ T细胞和CD20+ B细胞），并使用数字图像分析软件QuPath在原发肿瘤的不同区域进行定量：肿瘤中心（TC）、内缘（IM）、外缘（OM）和瘤周（PT）区域。样本来自36例mRCC-cc患者，这些患者一线接受TKIs治疗，二线或三线序贯接受nivolumab治疗。使用单变量和多变量Cox回归模型评估免疫细胞密度、临床病理特征与生存结局之间的关联。评估了无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。 结果：所有免疫细胞的密度在OM和PT区域均显著高于TC和IM区域。年龄较大与较低的CD8+ T细胞和CD20+ B细胞密度相关，而较高的肿瘤分级与IM中CD20+ B细胞浸润增加相关。IM和OM中高CD20+ B细胞密度与一线TKI治疗期间较短的PFS显著相关（风险比（HR）= 3.30，P = 0.015和HR = 3.25，P = 0.016）。相比之下，PT区域中等密度的CD8+ T细胞与序贯nivolumab治疗期间更长的PFS相关（HR = 0.26，P = 0.007）。未观察到免疫细胞密度与ORR或OS之间存在显著关联。结论：我们的研究结果表明，肿瘤浸润CD20+ B细胞的空间定位和密度是TKIs治疗中PFS不良的潜在预测因素，而瘤周区域较高的CD8+ T细胞浸润可能是nivolumab治疗中PFS延长的潜在预测因素。这些基于免疫细胞的参数可能完善预后模型，并有助于指导mRCC-cc的治疗选择。
Background : Tumor-infiltrating lymphocytes (TILs) are known to influence disease progression and treatment response in clear cell renal cell carcinoma. This study aimed at evaluating the prognostic and predictive relevance of T and B cell infiltration patterns in patients with metastatic clear cell renal cell carcinoma (mRCC-cc) treated sequentially with tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitor nivolumab. Methods : In this retrospective cohort study, immune cell densities (CD3+, CD8+ T cells and CD20+ B cells) were analyzed by immunohistochemistry and quantified using digital image analysis software QuPath in distinct tumor regions of primary tumor: tumor center (TC), inner margin (IM), outer margin (OM), and peritumoral (PT) region. Samples were obtained from 36 patients with mRCC-cc treated with TKIs in the first line and sequentially with nivolumab in the second or third-line setting. Associations between immune cell densities, clinicopathological features, and survival outcomes were assessed using univariable and multivariable Cox regression models. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. Results : Densities of all immune cells were significantly higher in the OM and PT regions than in the TC and IM. Older age correlated with lower CD8+ T cell and CD20+ B cell densities, whereas higher tumor grade was associated with increased CD20+ B cell infiltration in IM. High CD20+ B cell density in IM and OM was significantly associated with shorter PFS during first-line TKI therapy (hazard ratio (HR) = 3.30, P = 0.015 and HR = 3.25, P = 0.016, respectively). In contrast, an intermediate CD8+ T cell density in the PT region was associated with longer PFS during sequential nivolumab treatment (HR = 0.26, P = 0.007). No significant associations between immune cell densities and ORR or OS were observed. Conclusions : Our findings suggest that spatial localization and density of tumor-infiltrating CD20+ B cells are potential predictors of poor PFS on TKIs, whereas higher CD8+ T cell infiltration in peritumoral areas may be a potential predictor of prolonged PFS on nivolumab. These immune-cell-based parameters may refine prognostic models and help guide treatment selection in mRCC-cc.
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