Dysregulation in immune functions isreflected in tumor cell cytotoxicity by peripheral blood mononuclearcells from head and neck squamous cell carcinoma patients

摘要

We assessed the immunological status of stage III and IV head and neck squamous cell carcinoma (HNSCC) patients and age-matched healthy individuals. In HNSCC patients, the total leukocyte count was lower and the proliferating ability of PBMCs against phytohemagglutinin (PHA) was significantly downregulated. These cells showed lower expression of the early activation marker CD69. Within this PBMC population, the proportion of CD4+, CD8+ T cells, CD3- CD56+, CD16+ NK cells and CD3+ CD56+ NK-T cells was seriously downregulated. However, the proportion of CD4+ CD25+ Foxp3+ regulatory T cells having suppressor function was upregulated. Other immune cells, like CD14+ monocytes/macrophages and CD20+ B cells, were also fewer in number, although this difference was not statistically significant. Assessment of the cytokine secretory status of PBMCs revealed suppressed levels of Th1 cytokines (IFN-γ, IL-12 and TNF-α) and elevated secretion of Th2 cytokines (IL-4 and IL-10) for HNSCC PBMCs whereas just the opposite was seen for PBMCs from healthy individuals. Dysregulation in the profile of immunocompetentcells and cytokine secretion was reflected in the suppressed cytotoxicfunction of HNSCC PBMCs, as tested on KB (oral cancer), MCF7 (breastcancer), COLO205 (colon cancer), Jurkat (T cell leukemia), K562 (erythroleukemia)and U937 (monocytic lymphoma) cell lines. The observed decreasedcytotoxicity of HNSCC PBMCs may be due to the downregulated expressionof cytotoxic molecules (perforin, granzymeB and FasL) in HNSCC PBMCs.Assessment of the extent of immune dysfunction might help designimmunotherapeutic protocols by incorporating any agent having immunomodulatory function.