Neutrophil-to-Lymphocyte Ratio and Intratumoral CD45RO-Positive T Cells as Predictive Factors for Longer Survival of Patients with Colorectal Liver Metastasis after Hepatectomy

Neutrophil-to-Lymphocyte Ratio and Intratumoral CD45RO-Positive T Cells as Predictive Factors for Longer Survival of Patients with Colorectal Liver Metastasis after Hepatectomy

TAKEOMI HAMADA,¹ HIDENOBU ISHIZAKI,¹ YUKIHIRO HARUYAMA,² ROKO HAMADA,¹ KOICHI YANO,¹ KAZUHIRO KONDO,¹ HIROAKI KATAOKA² and ATSUSHI NANASHIMA¹

¹Department of Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Miyazaki, Japan
²Department of Pathology, University of Miyazaki Faculty of Medicine, Miyazaki, Miyazaki, Japan

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.

Keywords —— colorectal liver metastasis; hepatectomy; host immunological response; survival; tumor-infiltrating lymphocytes

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Tohoku J. Exp. Med., 2020, 251, 303-311

Correspondence: Atsushi Nanashima, M.D., Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Kiyotake-cho, Miyazaki, Miyazaki 889-1692, Japan.

e-mail: a_nanashima@med.miyazaki-u.ac.jp