M2 macrophages and regulatory T cells in lethal prostate cancer
M2 macrophages and regulatory T cells in lethal prostate cancer
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DOI：
10.1002/pros.23742
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发表时间：
2019-03-01
期刊：
影响因子：
2.8
通讯作者：
Davidsson, Sabina
中科院分区：
文献类型：
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作者：
Erlandsson, Ann;Carlsson, Jessica;Davidsson, Sabina
前列腺癌（PCa）是世界上最常见的癌症之一。新出现的证据表明，炎症细胞如M2巨噬细胞和调节性T细胞（T-regs）可以通过抑制抗肿瘤免疫反应来促进癌症的进展。本研究研究了前列腺癌组织中cd163阳性M2巨噬细胞的数量。研究了M2巨噬细胞与T-regs的相关性和相互作用。方法：本巢式病例对照研究纳入了经尿道前列腺切除术时偶然发现的前列腺癌男性队列。225例死于前列腺癌的男性，367例在前列腺癌诊断后存活超过10年且无疾病进展的男性作为对照。采用免疫组化方法对PCa组织中浸润的cd163阳性M2巨噬细胞和FOXP3/ cd4阳性T-regs细胞进行检测。分别采用Spearman秩序相关和似然检验评估M2巨噬细胞与T-regs的相关性和相互作用。使用逻辑回归来估计致死PCa和巨噬细胞计数的比值比（ORs）。结果M2巨噬细胞数量与T-regs呈显著相关（P < 0.001），但无相互作用。M2巨噬细胞数量高的男性致死性PCa的OR为1.93 （95%CI: 1.23-3.03）。同样，对于预后不确定的病例（GS分类3 + 4和4 + 3），M2巨噬细胞数量高确实预示着预后较差。结论我们的数据显示前列腺肿瘤环境中M2巨噬细胞数量高的男性死于前列腺癌的几率增加。M2巨噬细胞可能与其他抑制细胞如T-regs一起促进免疫抑制环境。
Background Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (T-regs) can contribute to cancer progression by suppressing the anti-tumor immune response. This study investigated the number of CD163-positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and T-regs. Methods This nested case-control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163-positive M2 macrophages and FOXP3/CD4-positive T-regs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and T-regs were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts. Results The number of M2 macrophages and T-regs showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis. Conclusions Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as T-regs, promote an immunosuppressive environment.