George Malietzis1,2, Gui Han Lee1,2,3, David Bernardo1, Alexandra I F Blakemore4, Stella C Knight1, Morgan Moorghen3, Hafid O Al-Hassi1, John T Jenkins2. 1. Antigen Presentation Research Group, Imperial College London, North West London Hospitals Campus, Watford Road, Harrow HA1 3UJ, UK. 2. Department of Surgery St. Marks Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, UK. 3. Department of Histopathology St. Marks Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, UK. 4. Section of Investigative Medicine, Division of Diabetes, Endocrinology, and Metabolism, Faculty of Medicine, Imperial College, London W12 0NN, UK.
Abstract
BACKGROUND AND OBJECTIVES: The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. METHODS: A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. RESULTS: High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). CONCLUSIONS: Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker.
BACKGROUND AND OBJECTIVES: The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. METHODS: A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. RESULTS: High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). CONCLUSIONS: Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker.
Authors: Bette J Caan; Elizabeth M Cespedes Feliciano; Carla M Prado; Stacey Alexeeff; Candyce H Kroenke; Patrick Bradshaw; Charles P Quesenberry; Erin K Weltzien; Adrienne L Castillo; Taiwo A Olobatuyi; Wendy Y Chen Journal: JAMA Oncol Date: 2018-06-01 Impact factor: 31.777
Authors: Austin J Barmore; Sally M Castex; Brittany A Gouletas; Alex J Griffith; Slater W Metz; Nicolas G Muelder; Michael J Populin; David M Sackett; Abigail M Schuster; Christopher T Veldkamp Journal: Biochem Biophys Res Commun Date: 2016-06-21 Impact factor: 3.575