Monocyte CD40 expression in head and neck squamous cell carcinoma (HNSCC).

CD40, an antigen-presenting cell expressed costimulatory receptor molecule, binds to T cell expressed CD40-ligand (CD40-L). Using a mouse tumor model, we showed previously that lower CD40/CD40-L expression levels promoted tumor growth whereas higher CD40/CD40-L expression levels led to tumor regression indicating duality in CD40 functions. Whether CD40/CD40-L expressions are regulated in cancer patients is unknown. Herein, we show that the CD40 and CD40-L expressions on monocytes and T cells, respectively, decrease as the head and neck squamous cell carcinoma (HNSCC) patients progress from stage-I through stage-IV suggesting a novel CD40/CD40-L expression based staging of HNSCC tumor. The staging is confirmed by TNM and histo-pathological staging. The levels of soluble CD40 (sCD40) and sCD40-L are also modulated in patients' plasma. As CD40 expressing monocytes increase in the post-operative patients, CD40 expression levels are possibly regulated by tumor load. This change is accompanied by increased IL-12 expressing monocytes and decreased IL-10 expression levels. Thus, our findings on CD40/CD40-L expression in HNSCC patients bear significant implications.