Smoking-, Alcohol-, and Age-Related Alterations of Blood Monocyte Subsets and Circulating CD4/CD8 T Cells in Head and Neck Cancer

SIMPLE SUMMARY: The formation of head and neck squamous cell carcinoma (HNSCC) is closely associated with cigarette smoking, alcohol abuse, and aging, but the immunologic alterations of peripheral monocytes and T-cells within this process are not fully understood. We aimed to investigate the impact of these factors on the abundances and characteristics of monocytes and CD4/CD8 T-cell subsets in the peripheral blood. Our data revealed distinct impacts of the individual behavior and age on the dynamics of these circulating immune cell subsets in head and neck cancer patients. ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. Although cigarette smoking, alcohol abuse, and aging are well-established associated factors for HNSCC, their respective influence on immunologic alterations of monocyte subsets or T-cell compositions in the peripheral blood has not yet been fully unveiled. Using flow cytometry, whole blood measurements of CD14/CD16 monocyte subsets and analyses of T-cell subsets in isolated PBMC fractions were carried out in 64 HNSCC patients in view of their tobacco and alcohol consumption, as well as their age, in comparison to healthy volunteers. Flow cytometric analysis revealed significantly increased expression of monocytic CD11b, as well as significantly decreased expression levels of CX3CR1 on classical and intermediate monocyte subsets in smoking-related and in alcohol-related HNSCC patients compared to healthy donors. Peripheral monocytes revealed an age-correlated significant decrease in PD-L1 within the entirety of the HNSCC cohort. Furthermore, we observed significantly decreased abundances of CD8(+) effector memory T cells in active-smoking HNSCC patients and significantly increased percentages of CD8(+) effector T cells in alcohol-abusing patients compared to the non-smoking/non-drinking patient cohort. Our data indicate an enhanced influence of smoking and alcohol abuse on the dynamics and characteristics of circulating monocyte subsets and CD4/CD8 T-cell subset proportions, as well as an age-related weakened immunosuppression in head and neck cancer patients.