Xu Le, Zhu Yu, Chen Lian, An Huimin, Zhang Weijuan, Wang Guomin, Lin Zongming, Xu Jiejie
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Ann Surg Oncol. 2014 Sep;21(9):3142-50. doi: 10.1245/s10434-014-3601-1. Epub 2014 Mar 11.
As the most abundant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are significant for fostering tumor progression. CD68(+) TAMs display diversely polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2). The aim of this study was to determine the survival impact of diametrically polarized TAMs in clear-cell renal cell carcinoma (ccRCC) and their application to stratification of patients according to their prognostic values.
The study included 185 consecutive patients with ccRCC who underwent nephrectomy between 1999 and 2001. CD68(+) total and diametrically polarized (CD11c(+) M1 and CD206(+) M2) TAM densities were assessed by immunohistochemistry, and the relationships with clinicopathologic features and prognosis were evaluated.
Low CD11c(+) TAM density and high CD206(+) TAM density were associated with reduced cancer-specific survival (P = 0.043 and P = 0.017, respectively), whereas CD68(+) TAM density only had borderline prognostic significance (P = 0.062). Furthermore, combined analysis of CD11c(+) and CD206(+) TAMs (CD11c/CD206 signature) had a better power to predict patients' outcome (P = 0.010). Together with TNM stage, tumor necrosis, and performance status, CD11c/CD206 signature was an independent prognostic factor (P = 0.010). When applied to the University of California Integrated Staging System intermediate-/high-risk group for localized ccRCC, CD11c/CD206 signature could further distinguish patients with dismal prognosis (P = 0.004).
Intratumoral balance of diametrically polarized TAMs is a novel independent predictor for survival in patients with ccRCC. Tipping the balance toward an antitumoral phenotype might be a promising target of postoperative adjuvant therapy.
作为最丰富的肿瘤浸润免疫细胞，肿瘤相关巨噬细胞（TAM）对促进肿瘤进展具有重要意义。CD68(+) TAM表现出不同的极化程序，包括CD11c(+)促炎巨噬细胞（M1）和CD206(+)免疫抑制巨噬细胞（M2）。本研究的目的是确定在透明细胞肾细胞癌（ccRCC）中完全极化的TAM对生存的影响，以及它们根据预后价值在患者分层中的应用。
该研究纳入了1999年至2001年间连续接受肾切除术的185例ccRCC患者。通过免疫组织化学评估CD68(+)总TAM和完全极化（CD11c(+) M1和CD206(+) M2）TAM的密度，并评估其与临床病理特征和预后的关系。
低CD11c(+) TAM密度和高CD206(+) TAM密度与癌症特异性生存率降低相关（分别为P = 0.043和P = 0.017），而CD68(+) TAM密度仅具有临界预后意义（P = 0.062）。此外，CD11c(+)和CD206(+) TAM的联合分析（CD11c/CD206特征）对预测患者预后具有更好的能力（P = 0.010）。与TNM分期、肿瘤坏死和体能状态一起，CD11c/CD206特征是一个独立的预后因素（P = 0.010）。当应用于加利福尼亚大学综合分期系统中局部ccRCC的中/高危组时，CD11c/CD206特征可进一步区分预后不良的患者（P = 0.004）。
完全极化的TAM在肿瘤内的平衡是ccRCC患者生存的一种新的独立预测指标。使平衡向抗肿瘤表型倾斜可能是术后辅助治疗的一个有前景的靶点。
