Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.
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DOI：
10.1371/journal.pone.0136654
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Scambia G
中科院分区：
文献类型：
--
作者：
Petrillo M;Zannoni GF;Martinelli E;Pedone Anchora L;Ferrandina G;Tropeano G;Fagotti A;Scambia G
我们研究了接受放化疗 (CT/RT) 治疗的局部晚期宫颈癌 (LACC) 患者中 1 型 (M1) 和 2 型 (M2) 肿瘤相关巨噬细胞 (TAM) 的治疗前比率的预后作用。对 84 名连续接受基于顺铂的 CT/RT 治疗、总剂量为 50.0 Gy、随后进行根治性手术的 LACC 患者进行了分析。对诊断时采集的肿瘤样本进行 CD163/p-STAT、CD68/pSTAT1、CD163/c-MAF 和 CD68/c-MAF 的双重染色免疫组织化学。具有 CD163+pSTAT1+ 或 CD68+pSTAT1+ 的 TAM 被定义为 M1； CD163+c-MAF+ 或 CD68+c-MAF+ 定义了 M2 表型。通过评估每个病例的相同肿瘤区域，在低放大倍数下对 M1 和 M2 细胞的数量进行计数。最终计算出M1和M2之间的比率（M1/M2）。在诊断时，我们观察到循环单核细胞数量与 TAM 数量之间存在直接相关性（p 值 = 0.001）。与 M1/M2 低的病例相比，M1/M2 高的患者对 CT/RT 的完全病理缓解（无残留肿瘤）更常见（55.0% vs 29.5%；p 值 = 0.029）。在多变量分析中，M1/M2（OR = 2.067；p 值 = 0.037）成为 CT/RT 病理反应的独立预测因子。与 M1/M2 低的女性相比，M1/M2 高的女性的 5 年无病生存率（67.2% 对 44.3%；p 值 = 0.019）和 5 年总体生存率（69.3% 对 46.9%；p 值 = 0.037）更长。在多变量分析中，高 M1/M2 比率的存在与不利的生存结果独立相关。 TAM 向 M2 表型的极化（如较低的 M1/M2 比率所反映）是 CT/RT 反应不佳和 LACC 生存期较短的独立预测因子。
we investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT). 84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated. At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis. polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.