Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer

Dariusz Waniczek; Zbigniew Lorenc; Mirosław Śnietura; Mariusz Wesecki; Agnieszka Kopec; Małgorzata Muc-Wierzgoń

doi:10.1007/s00005-017-0463-9

Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer

Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):445-454. doi: 10.1007/s00005-017-0463-9. Epub 2017 Mar 25.

Authors

Dariusz Waniczek¹, Zbigniew Lorenc², Mirosław Śnietura³, Mariusz Wesecki², Agnieszka Kopec³, Małgorzata Muc-Wierzgoń⁴

Affiliations

¹ SHS in Katowice, Department of Propaedeutics Surgery, Chair of General, Colorectal and Polytrauma Surgery, Medical University of Silesia in Katowice, Żeromskiego 7, 41-902, Bytom, Poland.
² SHS in Katowice, Chair of General, Colorectal and Polytrauma Surgery, Medical University of Silesia in Katowice, Plac Medyków 1, 41-200, Sosnowiec, Poland.
³ Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Armii Krajowej 15, 44-100, Gliwice, Poland.
⁴ Department of Internal Medicine, Medical University of Silesia in Katowice, Żeromskiego 7, 41-902, Bytom, Poland. mwierzgon@sum.edu.pl.

Abstract

The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68⁺/iNOS^- and Tregs CD8⁺/FoxP3⁺ in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33-3.14; p = 0.001 and RR 2.08, 95% CI 1.28-3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44-27.9; p < 0.0001 and RR 12.5, 95% CI 4.9-32.4; p < 0.0001, respectively). Infiltration of TAMs CD68⁺/iNOS^- and Tregs CD8⁺/FoxP3⁺ in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC.

Keywords: Colorectal cancer; Regulatory lymphocytes; TAMs; Tregs; Tumor-associated macrophages.

MeSH terms

Adult
Aged
Aged, 80 and over
Cell Movement
Colonic Neoplasms / diagnosis
Colonic Neoplasms / immunology*
Colonic Neoplasms / mortality
Colorectal Neoplasms / diagnosis
Colorectal Neoplasms / immunology*
Colorectal Neoplasms / mortality
Female
Follow-Up Studies
Humans
Macrophages / immunology*
Male
Middle Aged
Neoplasm Staging
Predictive Value of Tests
Prognosis
Recurrence
Risk
Survival Analysis
T-Lymphocytes, Regulatory / immunology*
Treatment Outcome