Immunosuppression appears to be more frequent and more profound in patients with head and neck cancer. The immune impairment often observed in these patients is not restricted to the tumor site but presents itself as a systemic defect. The project aims at understanding the molecular mechanism of CD3 ζ chain degradation, both at the mRNA and protein level. Studies demonstrate a marked reduction in lymphocyte proliferative responses, calcium flux and a strong TH2 bias in OC patients. Results indicate a marked reduction in CD3-ζ chain expression in PBL of OC patients as compared to healthy individual (HI). The CD3-ζ defect was found to be T cell V beta subset-specific. The CD3-ζ mRNA and protein expression (flow cytometry and western blotting) decreased as the tumor stage increased. Studies demonstrate that ubiquitination is also responsible for the altered recycling and internalisation of the CD3 ζ chain receptor. The underlying reason for CD3 ζ chain transcriptional defect in tumor compartment is the decreased expression of CD3 ζ transcription factor Elf 1. Preliminary data indicates that the tumor-derived factor involved in CD3 ζ chain degradation is TNF alpha secreted by oral tumor cells. It has also been noted that patients undergoing a combination of surgery and radiotherapy show a marked increase in the expression of CD3 ζ chain in the peripheral blood compartment. An important outcome of the study is that we are now pursuing CD3 ζ as a biomarker for predicting prognosis of oral cancer.