CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[(18)F]FDG PET/CT.
Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[(18)F]FDG PET/CT.
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我们的研究结果表明，2-[18F]FDG PET/CT 可为 ccRCC 患者提供 TIME 的代谢信息，并据此制定影像引导的治疗策略。术前 SUVmax 升高的患者应予以重视，围手术期免疫治疗可能对他们有益。
如今，有必要非侵入性地探索与肿瘤免疫微环境（TIME）相关的有效生物标志物。在此，我们研究了术前2-[18F]FDG PET/CT的代谢参数是否能提供透明细胞肾细胞癌（ccRCC）患者TIME的相关信息。
回顾性分析了90例新诊断的ccRCC患者，这些患者在手术前接受了2-[18F]FDG PET/CT检查。免疫学特征包括TIL（肿瘤浸润淋巴细胞）（TILs）密度、程序性死亡配体1（PD-L1）表达和肿瘤免疫微环境类型（TIMTs）。TIMTs分为TIMT I（PD-L1阳性且TILs高）、TIMT II（PD-L1阴性且TILs低）、TIMT III（PD-L1阳性且TILs低）和TIMT IV（PD-L1阴性且TILs高）。分析了原发灶2-[18F]FDG PET/CT最大标准化摄取值（SUVmax）与免疫学特征之间的关系。采用Cox比例风险分析确定肾切除术后无病生存期（DFS）的预后因素。
高 TILs 浸润的肿瘤与 SUVmax 升高及侵袭性临床病理特征（如高 WHO/ISUP 分级）显著相关。肿瘤细胞上的 PD-L1 表达与 WHO/ISUP 分级呈正相关，与 BMI 呈负相关。然而，无论其空间组织分布如何，SUVmax 与 PD-L1 表达之间均未观察到相关性。TIMT I 和 IV 的 SUVmax 高于 TIMT II，但仅在 TIMT II 与 IV 之间存在显著差异。在多因素分析中，SUVmax（P = 0.022，HR 3.120，95% CI 1.175-8.284）和 WHO/ISUP 分级（P = 0.046，HR 2.613，95% CI 1.017-6.710）是 DFS 的显著预后因素。6 例（16.2%）SUVmax 正常的患者出现疾病进展，而 25 例（71.4%）SUVmax 升高的患者出现疾病进展。相反，免疫学特征无预后价值。
Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[ 18 F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC).
Ninety patients with newly diagnosed ccRCC who underwent 2-[ 18 F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[ 18 F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy.
Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value.
Our findings demonstrated that 2-[ 18 F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.
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