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Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients
Author(s) -
Aarstad Hans Jørgen,
Vintermyr Olav K.,
Ulvestad Elling,
Aarstad Helene H.,
Kross Kenneth W.,
Heimdal John. H.
Publication year - 2015
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12356
Subject(s) - medicine , monocyte , head and neck squamous cell carcinoma , lymphocyte , head and neck cancer , prospective cohort study , cancer , gastroenterology , oncology , flow cytometry , immunology , pathology
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 CD 69 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 CD 69 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 CD 69 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 CD 69 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.