Change in CD3ζ‐chain expression is an independent predictor of disease status in head and neck cancer patients

Abstract

CD3f has emerged as a clinically important immunological marker in head and neck squamous cell carcinoma (HNSCC) with reduced level of expression reported in both tumor infiltrating lymphocytes and peripheral blood lymphocytes. In this prospective study (power 5 0.99, a 5 0.05), CD3f expression was compared in 47 HNSCC patients and 53 controls using standardized flow cytometric method. There was no statistical difference in the percentages of the CD3 e1 T-cell subset present in the peripheral blood mononuclear cells of the HNSCC patients and the healthy controls; however, T cells from the HNSCC patients produced a significantly weaker IFN-c response in comparison to the healthy controls, when they were stimulated by the recall viral CEF peptide antigen. All patients were followed up for at least 3 years with a median follow-up of 45 months. Levels of CD3f-chain expression were measured at 117 follow-up visits at six-month intervals. Receiver operating characteristic curve identified the optimal cut off as a 12% increase in post treatment CD3f-chain expression from the baseline levels to confirm absence of HNSCC with the area under curve of 0.81 (95% CI 5 0.68-0.94) for predicting absence of HNSCC. The specificity, sensitivity and positive predictive value were 81.25% 79.21% and 97.56%, respectively. Three-year disease specific survival (DSS) was significantly lower (p 5 0.007) at 63.2% for patients who showed <12% increase in CD3f-chain level as compared to 96.2% for patients who had 12% increase. Our results indicate that the change in CD3f-chain expression from the baseline is an independent predictor of residual and recurrent HNSCC.

Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma

“…These alterations, along with other mechanisms, are responsible for deficient immune responsiveness of T-cells in cancer patients, including OvCa 46,47 . Importantly, the CD3ζ chain loss in T-cells of cancer patients is biologically significant, as it correlates with worse prognosis and shorter OS, as reported for OvCa 33 , head and neck cancer 48 , and breast cancer 49 . We and others have shown previously that tumor-derived microvesicles, including exosomes in OvCa, suppress CD3ζ chain expression of T-cells 50,51 , but identified no responsible mechanism.…”

Identification of a Prognostic Signature for Ovarian Cancer Based on the Microenvironment Genes

“…In cervical carcinoma, low expression of CD3E was correlated with poor disease-specific and disease-free survival, and high CD3E expression was correlated with improved disease-specific survival ( Punt et al, 2015 ). Moreover, this gene was also considered as a hub gene in head and neck squamous cell carcinoma ( Upreti et al, 2016 ). A high expression of GBP4 was correlated with favorable overall survival in skin (cutaneous) melanoma patients followed for over 30 years ( Wang et al, 2018 ).…”

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

“…With the decrease in the expression of the CD3ζ chain, the functions of T cells, such as proliferative ability, cytotoxic activity, and cytokine production are inhibited, finally suppressing the immune response [46][47][48]. In line with this, the reduced expression of CD3ζ has been reported in several cancers, such as gastric adenocarcinoma, breast cancer, and head and neck cancer [49][50][51]. In the tumor microenvironment, granulocytic or polymorphonuclear myeloid-derived suppressor cells, which are immunosuppressive cells, have the ability to overexpress ROS to inhibit T-cell activation and function, thus promoting tumor metastasis [18].…”