Department of Surgery, University of Miyazaki Faculty of Medicine.
Department of Pathology, University of Miyazaki Faculty of Medicine.
Tohoku J Exp Med. 2020 Aug;251(4):303-311. doi: 10.1620/tjem.251.303.
Colorectal cancer is the fourth most common malignancy across the world, and over 50% of patients had colorectal liver metastases (CLM). Activated neutrophils and tumor-infiltrating lymphocytes (TILs) are considered to interrupt progression of primary colorectal cancer; however, immunological host reactions to CLM have not been fully elucidated. We thus aimed to explore the prognostic implication of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and TILs in resected metastatic cancer tissues of 29 patients with CLM who underwent hepatectomy. To evaluate local immunological responses in CLM, we examined the infiltration of CD66b+ neutrophils and TILs, such as CD8+ T cells, CD45RO+ T cells, and forkhead box P3+ (FOXP3+) T cells. The presence of fewer than 4 tumors (p = 0.0005), the absence of distant metastasis (p = 0.018), adjuvant anti-cancer chemotherapy (p = 0.0013), and elevated NLR over 4.1 (p = 0.026) were found to be significant parameters related to longer survival after hepatectomy. Further, high numbers of infiltrated CD45RO+ T cells in CLM were significantly associated with longer patient survival (p = 0.020). The numbers of CD45RO+ T cells were correlated with those of CD8+ T cells (p = 0.008). The numbers of peripheral blood neutrophils were negatively correlated with those of CD45RO+ T cells (p = 0.038) and of CD66b+ neutrophils (p = 0.008) in CLM. The present data indicate that elevated peripheral blood NLR and high numbers of intratumoral CD45RO+ T cells are predictive of longer CLM patient survival after hepatectomy among current biomarkers.
结直肠癌是全球第四大常见恶性肿瘤,超过 50%的患者有结直肠肝转移(CLM)。活化的中性粒细胞和肿瘤浸润淋巴细胞(TIL)被认为可以阻止原发性结直肠癌的进展;然而,CLM 的免疫宿主反应尚未完全阐明。因此,我们旨在探索 29 例接受肝切除术的 CLM 患者外周血中性粒细胞与淋巴细胞比值(NLR)和切除转移性癌组织中 TIL 的预后意义。为了评估 CLM 的局部免疫反应,我们检查了 CD66b+中性粒细胞和 TIL 的浸润,如 CD8+T 细胞、CD45RO+T 细胞和叉头框 P3+(FOXP3+)T 细胞。发现存在少于 4 个肿瘤(p=0.0005)、无远处转移(p=0.018)、辅助抗癌化疗(p=0.0013)和 NLR 高于 4.1(p=0.026)是与肝切除术后生存时间延长相关的显著参数。此外,CLM 中浸润的 CD45RO+T 细胞数量较高与患者生存时间延长显著相关(p=0.020)。CD45RO+T 细胞数量与 CD8+T 细胞数量相关(p=0.008)。外周血中性粒细胞数量与 CLM 中 CD45RO+T 细胞(p=0.038)和 CD66b+中性粒细胞(p=0.008)数量呈负相关。本研究数据表明,在目前的生物标志物中,外周血 NLR 升高和肿瘤内 CD45RO+T 细胞数量增加与 CLM 患者肝切除术后生存时间延长相关。