CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Prognostic and predictive significance of GITR in metastatic renal cell carcinoma.
Prognostic and predictive significance of GITR in metastatic renal cell carcinoma.
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在转移性 RCC 患者中，较高的 GITR 与更好的 PFS 相关。
近年来肾细胞癌（RCC）逐渐增多。随着免疫检查点抑制剂引入，转移性 RCC 治疗取得显著进展。糖皮质激素诱导的肿瘤坏死因子（TNF）受体相关蛋白（GITR）是一种共刺激分子，在活化 CD4⁺ T 淋巴细胞、CD8⁺ T 淋巴细胞及叉头框蛋白 3（FOXP3）阳性调节性 T 细胞（Treg）中表达水平最高。GITR 可增加白细胞介素（IL）-2、CD25 和干扰素 γ；通过抑制 FOXP3⁺ Treg 的免疫抑制功能发挥抗肿瘤作用。因此，本研究旨在评估 GITR、TIL（肿瘤浸润淋巴细胞）（CD4⁺/CD8⁺ TIL）和 FOXP3 在转移性 RCC 患者中的预后及预测价值。
研究纳入 2016 至 2021 年经病理确诊的转移性肾癌患者，记录临床病理特征及部分实验室检查结果，并通过免疫组化对活检或肾切除标本中的 GITR、CD4、CD8 和 FOXP3 进行评估。
共纳入 41 例患者。中位无进展生存期（PFS）为 10.5 个月，中位总生存期（OS）为 13.9 个月。GITR 低表达组中位 PFS 为 7.9 个月，高表达组为 18.9 个月；高表达组 PFS 显著更长（p = 0.003）。在接受二线 nivolumab 的患者中，GITR 低表达组中位 PFS 为 5.7 个月，高表达组为 15.7 个月；高表达组 PFS 显著更长（p = 0.026）。
转移性 RCC 患者 GITR 表达较高与更好的 PFS 相关。接受 nivolumab 治疗患者中，GITR 高表达组 PFS 也较好。如前瞻性研究证实，GITR 可同时作为预后和预测标志物。
Renal cell carcinoma (RCC) has gradually increased in recent years. There have been significant developments in metastatic RCC in recent years with the introduction of immune control point inhibitors. Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) is a co-stimulatory molecule and is seen in the highest amounts in activated CD4+ T lymphocytes and CD8+ T lymphocytes, forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg). GITR leads to an increase in interleukin (IL)-2 and CD25 and Interferon Gamma. It shows an anti-tumoural effect by inhibiting the suppressive functions of FOXP3+ regulatory cells (Treg). Therefore, we aimed to evaluate the prognostic and predictive effect of GITR, tumor-infiltrating lymphocytes (CD4+CD8) (TIL), and FOXP3 in patients with metastatic RCC.
Patients diagnosed with pathologically confirmed metastatic renal cancer between 2016 and 2021 were included in our study. Clinicopathological features and some laboratory tests were recorded. GITR, CD4, CD8, and FOXP3 were evaluated by immunohistochemistry (IHC) from biopsies or nephrectomy material and recorded.
The study included 41 patients. The median progression-free survival (PFS) was 10.5 months, and the median overall survival (OS) was 13.9 months. Median PFS was 7.9 months for the GITR-low group and 18.9 months for the GITR-high group. Median PFS was statistically significant and longer for the GITR-high group than the GITR-low group (p=0.003). When patients who received nivolumab in the 2nd line were evaluated, median PFS was found to be 5.7 months in the GITR-low group and 15.7 months in the GITR-high group. Median PFS was statistically significantly higher in the GITR-high group than in the GITR-low group (p=0.026).
In patients with metastatic RCC, higher GITR was associated with better PFS. At the same time, in patients using nivolumab, better PFS was seen in the GITR high group. If supported by prospective studies, GITR can be used as both a prognostic and predictive marker.
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