Department of Surgery, Tokai University School of Medicine, Isehara, Japan.
Department of Surgery, Tokai University School of Medicine, Isehara, Japan,
Oncology. 2020;98(12):869-875. doi: 10.1159/000508922. Epub 2020 Aug 14.
Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision surgery is a standard treatment for locally advanced rectal cancer (LARC). Tumor-infiltrating lymphocytes (TILs) have been reported to be associated with tumor response; however, this remains to be established. We previously reported that histological changes on biopsy specimens obtained 7 days after starting nCRT are strong predictors of response to nCRT.
The subjects were 208 patients with LARC who received nCRT. TILs on hematoxylin-eosin staining together with immunohistochemical staining of lymphocyte surface markers including CD3, CD4, CD8, and FoxP3 were performed both on the biopsy specimens before and 7 days after starting nCRT.
The proportions of patients with high densities of CD3+, CD4+, CD8+, and FoxP3+ cells 7 days after starting CRT were significantly lower than the respective values before starting nCRT (p < 0.0001, p < 0.0001, p = 0.0023, and p = 0.0046). In biopsy specimens obtained before treatment, high-density CD4+ cells and FOXP3+ cells were significantly associated with tumor shrinkage rate. High-density FOXP3+ cells were significantly associated with marked tumor regression. In biopsy specimens obtained 7 days after starting treatment, high-density CD4+ cells were significantly associated with marked tumor regression, tumor regression grade 1, and tumor shrinkage rate. High-density FoxP3+ cells were significantly associated with marked tumor regression and tumor shrinkage rate.
In patients who received nCRT for LARC, the evaluations of immunohistochemical staining for CD4+ and FOXP3+ TILs were more intimately related to histological response to CRT and tumor shrinkage rates in biopsy specimens obtained 7 days after starting treatment than in biopsy specimens obtained before CRT.
新辅助放化疗（nCRT）后行全直肠系膜切除术是局部晚期直肠癌（LARC）的标准治疗方法。肿瘤浸润淋巴细胞（TILs）已被报道与肿瘤反应相关，但这仍有待证实。我们之前报道过，nCRT 开始后 7 天获得的活检标本的组织学变化是预测 nCRT 反应的有力指标。
本研究纳入了 208 例接受 nCRT 的 LARC 患者。对 nCRT 开始前后的活检标本进行苏木精-伊红染色和淋巴细胞表面标志物（包括 CD3、CD4、CD8 和 FoxP3）的免疫组织化学染色，以检测 TILs。
nCRT 开始后 7 天 CD3+、CD4+、CD8+和 FoxP3+细胞高密度的患者比例明显低于 nCRT 开始前（p<0.0001、p<0.0001、p=0.0023 和 p=0.0046）。在治疗前的活检标本中，高密度 CD4+细胞和 FOXP3+细胞与肿瘤退缩率显著相关。高密度 FOXP3+细胞与明显的肿瘤消退显著相关。在 nCRT 开始后 7 天获得的活检标本中，高密度 CD4+细胞与明显的肿瘤消退、肿瘤消退分级 1 和肿瘤退缩率显著相关。高密度 FoxP3+细胞与明显的肿瘤消退和肿瘤退缩率显著相关。
在接受 nCRT 治疗的 LARC 患者中，CD4+和 FOXP3+TILs 的免疫组织化学染色评估与 nCRT 后活检标本的组织学反应和肿瘤退缩率更为密切相关，而与 nCRT 前活检标本的相关性较小。
