Department of Health Toxicology, Second Military Medical University, Shanghai 200433, China.
Department of Environmental Hygiene, Second Military Medical University, Shanghai 200433, China.
Cancer Med. 2018 May;7(5):1731-1741. doi: 10.1002/cam4.1420. Epub 2018 Mar 24.
The polarization of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), especially from the antitumoral phenotype to the protumoral phenotype under certain conditions, has an important influence on the progression of tumors. However, the interactions and combined prognosis of these cells are poorly known. Here, we detected the infiltration of CD68 TAMs, CD163 TAMs, and CD66b TANs in the specimens from 662 patients with GC by immunohistochemistry. The results showed that the infiltration of each of CD163 , CD68 , and CD66b cells in GC tissue was significantly increased and independently associated with GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the infiltration of CD163 and CD68 cells in GC, and multivariate Cox analysis confirmed the infiltration of CD163 cells was a better predictor for prognosis than that of CD68 cells. The combination of the infiltration of CD163 and CD66b cells provided more accurate survival prediction than any individual marker. Patient subgroups with CD66b CD163 (hazard ratio (HR) = 2.161; 95% confidence interval (CI) = 1.266-3.688; P < 0.001), CD66b CD163 (HR = 3.575; 95% CI = 2.155-5.933; P < 0.001), and CD66b CD163 (HR = 7.514; 95% CI = 4.583-12.312; P < 0.001) were gradually associated with shorter DFS when compared with the subgroup with CD66b CD163 . The similar result was also for DSS among the subgroups. Moreover, the two-marker model could more effectively discriminate the prognosis among the patients with chemotherapy than that among those without chemotherapy. We concluded that CD163 TAMs were a more valuable prognostic marker than CD68 TAMs, and CD163 TAMs combined with CD66b TANs could more precisely predict the prognosis of patients with GC.
肿瘤相关巨噬细胞（TAMs）和肿瘤相关中性粒细胞（TANs）的极化，特别是在某些条件下从抗肿瘤表型向促肿瘤表型的极化，对肿瘤的进展有重要影响。然而，这些细胞的相互作用和联合预后尚不清楚。在这里，我们通过免疫组织化学法检测了 662 例 GC 患者标本中 CD68 TAMs、CD163 TAMs 和 CD66b TANs 的浸润情况。结果表明，GC 组织中每种 CD163、CD68 和 CD66b 细胞的浸润均显著增加，并与 GC 预后独立相关。GC 组织中 CD163 和 CD68 细胞浸润之间存在很强的共线性（r=0.690，P<0.001），多变量 Cox 分析证实 CD163 细胞浸润是预后的更好预测因子，而不是 CD68 细胞浸润。CD163 和 CD66b 细胞浸润的组合比任何单个标志物提供更准确的生存预测。与 CD66b CD163（危险比（HR）=2.161；95%置信区间（CI）=1.266-3.688；P<0.001）、CD66b CD163（HR=3.575；95%CI=2.155-5.933；P<0.001）和 CD66b CD163（HR=7.514；95%CI=4.583-12.312；P<0.001）相比，患者亚组的 CD66b CD163、CD66b CD163 和 CD66b CD163 浸润与较短的无病生存期（DFS）逐渐相关。在亚组中，DFS 也存在类似的结果。此外，与无化疗患者相比，该两标志物模型能更有效地区分化疗患者的预后。我们得出结论，CD163 TAMs 是比 CD68 TAMs 更有价值的预后标志物，CD163 TAMs 与 CD66b TANs 联合可更精确地预测 GC 患者的预后。
