Prognostic value of circulating invariant NKT cell levels in patients with squamous cell carcinoma of the head and neck

Proc Amer Assoc Cancer Res, Volume 47, 2006 630 Invariant T Cell Receptor (TCR) Vα24+Vβ11+ Natural Killer T cells (iNKT) play an important role in immunoregulation via the secretion of cytokines (e.g. interferon (IFN)-γ and interleukin (IL)-4). Therapeutic activation of iNKT cells has potent anti-tumor effects in several metastatic disease models. We have previously demonstrated a numeric iNKT cell deficiency in peripheral blood of cancer patients. This defect was not secondary to tumor growth and the residual NKT cell population in these patients had retained the ability to secrete IFN-γ upon antigenic triggering. Therefore, the remaining NKT cells might still be involved in anti-tumor responses. Based on these findings we investigated here whether a greater defect in the circulating NKT cell pool in individual patients results in poorer prognosis. The number of circulating iNKT cells was determined by flowcytometric detection of the fraction of T lymphocytes co-expressing the TCR-Vα24 and TCR-Vβ11 chain, in peripheral blood samples taken prior to radiotherapy (RTH) of 48 patients with squamous cell carcinoma of the head and neck. Clinical data were obtained from a 56 months follow up period. Whereas the number of T or NK cells had no prognostic value, patients with a strongly diminished circulating iNKT cell fraction prior to RTH ( 231 iNKT/ 106 T cells) iNKT levels (mean = 32, 52 and 48 months respectively) (p = 0.0140, Log Rank test). Multivariate analysis revealed that disease specific survival (DSS) and locoregional control (LRC) were independent factors influencing OS. The prognostic value presented here strengthens the hypothesis that human iNKT cells prominently contribute to anti-tumor immune surveillance. This provides a promising strategy for the therapeutic intervention of metastatic disease, by the reconstitution of the circulating iNKT cell pool (e.g. via autologous adoptive transfer of ex-vivo expanded iNKT cells). Furthermore, screening for iNKT levels in peripheral blood samples is a non-invasive, straightforward and potentially efficient prognostic tool.