University of Leeds, Leeds, UK.
University of Leeds, Leeds, UK.
Lancet. 2015 Feb 26;385 Suppl 1:S87. doi: 10.1016/S0140-6736(15)60402-0.
Only half of patients with locally invasive rectal carcinoma respond to short-course preoperative radiotherapy. A predictive test enabling better patient selection could avoid unneccessary radiation exposure to poor responders. Macrophages within the tumour immune microenvironment with tumoricidal M1 and tumour-protective M2 phenotypes could be modulating this response. This study investigated the possible predictive value of M1 and M2 subpopulations in identifying patients' likely response to short-course preoperative radiotherapy.
Biopsy samples were taken from 29 patients with locally invasive rectal carcinoma before treatment with short-course radiotherapy and surgical specimens obtained after resection following short-course preoperative radiotherapy. Dual-staining immunohistochemistry was performed with CD68 as macrophage marker, HLA-DR as M1 marker, and CD163 as M2 marker. Samples were scored for hot-and-random spots by Nuance software (version 3.0.2) and compared with patients' outcome data. Tumour response was measured by assessment of reduction of tumour-cell density.
Samples revealing a low score for HLA-DR positive M1 macrophages exhibited a better response to short-course radiotherapy with up to 80% (median 80·38% [IQR 46·94-84·73]) reduction in the tumour cell density. On the other hand those with a high score exhibited a poor response with only up to 20% (20·26 [0-48·19]) reduction. The difference in response between the two groups was significant (p=0·017). No such trends were observed for CD163+ M2 macrophages. The ratio of HLA-DR+ to CD163+ macrophages for biopsy and resection samples was significantly different, showing a drop in the HLA-DR positive macrophages in the resection samples (p=0·024). The mean of the difference between the biopsy (median 2·53 [IQR 1·98-3·08]) and resection (1·38 [0·96-1·8]) was 1·15 (p=0·024).
Patients with a variable macrophage phenotype composition within biopsy samples from patients with locally invasive rectal carcinoma respond differently to short-course preoperative radiotherapy. Further investigation involving a panel of macrophage and other immune-cell markers could verify and validate these findings and develop them as predictive tests identifying good responders to radiotherapy in patients with locally invasive rectal carcinoma.
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只有一半局部侵袭性直肠癌患者对短程术前放疗有反应。一种能够更好地选择患者的预测性测试可以避免对不良反应者进行不必要的辐射暴露。肿瘤免疫微环境中的巨噬细胞具有细胞毒性 M1 和肿瘤保护性 M2 表型，可能调节这种反应。本研究探讨了 M1 和 M2 亚群在识别患者对短程术前放疗可能反应中的可能预测价值。
对 29 例局部侵袭性直肠癌患者在接受短程放疗前和短程术前放疗后切除标本时进行活检。采用 CD68 作为巨噬细胞标志物、HLA-DR 作为 M1 标志物、CD163 作为 M2 标志物进行双重免疫组织化学染色。使用 Nuance 软件（版本 3.0.2）对热区和随机区进行评分，并将评分与患者的预后数据进行比较。通过评估肿瘤细胞密度的减少来测量肿瘤反应。
HLA-DR 阳性 M1 巨噬细胞评分较低的样本对短程放疗有更好的反应，肿瘤细胞密度降低高达 80%（中位数 80·38%[46·94-84·73]）。另一方面，评分较高的样本反应较差，仅降低 20%（20·26%[0-48·19]）。两组间的反应差异有统计学意义（p=0·017）。对于 CD163+M2 巨噬细胞，未观察到类似趋势。活检和切除样本中 HLA-DR+与 CD163+巨噬细胞的比值明显不同，显示切除样本中 HLA-DR 阳性巨噬细胞减少（p=0·024）。活检（中位数 2·53[1·98-3·08]）和切除（1·38[0·96-1·8]）之间差值的平均值为 1·15（p=0·024）。
局部侵袭性直肠癌患者活检样本中巨噬细胞表型组成不同的患者对短程术前放疗的反应不同。进一步涉及巨噬细胞和其他免疫细胞标志物的研究可以验证和验证这些发现，并将其发展为预测性测试，以确定局部侵袭性直肠癌患者对放疗的良好反应者。
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