title: Peripheral blood monocyte and T-lymphocyte activation levels at diagnosis predict long-term survival in head and neck squamous cell carcinoma patients.
abstract: This study was performed to determine whether peripheral blood (PB) monocyte and/or lymphocyte activation at diagnosis were associated with long-term prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to what extent such prognostic properties relate to human papilloma virus (HPV)-associated tumor infection of the included patients. This was a long-term prospective study describing patient survival in relation to PB T lymphocyte and monocyte activation in patients observed for up to 14 years following diagnosis. Sixty-four patients from a consecutive cohort of newly diagnosed HNSCC patients along with 16 non-cancer control patients were included over a period of almost 2 years. Monocyte responsiveness was assessed at diagnosis (N = 56 HNSCC/16 non-cancer controls) by measuring net levels of spontaneous vs lipopolysaccharide-induced monocyte chemotactic protein (MCP)-1 secretion in vitro. PB T lymphocyte activation was determined (N = 58 HNSCC/16 controls) by measuring the percentage of T cells expressing CD69 by flow cytometry. Whether HPV infection or not was determined by PCR analysis on formalin fixed paraffin-embedded tumor tissue. Tumor HPV-positive patients had better prognosis than HPV-negative patients. A low net MCP-1 response in monocytes predicted increased survival (Relative risk (RR) = 2.1; Confidence interval (CI): 1.1-4.0; p < 0.05). A low percentage of CD69 positive T lymphocytes also predicted better prognosis (RR = 2.6; CI: 1.3-5.0; p = 0.005). The predictive power of MCP-1 monocyte and CD69 T lymphocyte measures were retained when adjusted for age and gender of the patients and shown to be independent of each other (N = 50 HNSCC/16 controls). The results were similar in HPV tumor-positive and -negative patients. Patients with high monocyte- and/or T lymphocyte activation status had low survival with 8% 5 year overall survival (OS) compared to 65% 5 year OS for patients with dual low activation levels (RR = 0.27; CI: 0.14-0.56; p < 0.001), mostly secondary to disease-specific survival. Both tumor HPV-positive and -negative HNSCC patients with high percentage of CD69 positive T lymphocytes and/or high monocyte MCP-1 secretion had low long-term survival. The data suggest that the general inflammatory and adaptive immune systems are independently linked to the clinical aggressiveness of both tumor HPV-negative and -positive HNSCC patients.
authors: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway; Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors: Hans Jørgen
authors: HJ
authors: Aarstad
authors: Olav K
authors: OK
authors: Vintermyr
authors: Elling
authors: E
authors: Ulvestad
authors: Helene H
authors: HH
authors: Aarstad
authors: Kenneth W
authors: KW
authors: Kross
authors: John H
authors: JH
authors: Heimdal
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018932:Chemokine CCL2; D058847:Inflammasomes; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C111835:CCL2 protein, human
keywords: Head and neck cancer; T lymphocyte; immunology; monocyte; neoplasms; prognosis