Abstract
The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs.
Highlights
Both epidemiological and experimental evidence suggest a link between chronic inflammation and the development of malignancy [1, 2], in particular when the inflammation is caused by chronic infection [3]
We have shown that a high IL-6 secretion measured from lipopolysaccharide (LPS)-stimulated peripheral blood (PB) monocytes from head and neck squamous cell carcinoma (HNSCC) patients predicted an impaired intermediate-term prognosis [19]
We have studied the prognosis of newly diagnosed HNSCC patients dependent on the spontaneous activation of T lymphocytes in vivo, and the level of monocyte priming in vitro from the same patients
Summary
Both epidemiological and experimental evidence suggest a link between chronic inflammation and the development of malignancy [1, 2], in particular when the inflammation is caused by chronic infection [3]. Chronic inflammation has been suggested to promote head and neck squamous cell carcinoma (HNSCC) [4]. The immune system probably takes part in the eradication of HPV-positive (+) tumor cells during treatment [8]. The role of the immune system in cases where HNSCC disease is caused by HPV infection beyond this finding is not well established. The potentially different roles of the immune system in HPV-negative (-) versus HPV-positive HNSCC patients have not been established and are of interest to study
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