Normal interleukin (IL)-7, IL-12 and IL-15 plasma levels were found. In one of the patients sporadic NK T cells were detected at the tumour site. α-Galactosylceramide (αGalCer) stimulation of peripheral blood mononuclear cells or isolated NK T cell lines from both patients induced IFN-γ, but no IL-4 and no response towards autologous tumour RXDX-106 cost cells or lysates. The clinical course of disease in both patients was not exceptional with regard to histological subtype and extent of metastatic disease. Therefore, despite a constitutive high peripheral frequency

and in vitroαGalCer responsiveness, the NK T cells in the two RCC patients did not show anti-tumour responsiveness. Invariant NK T cells are a distinct set of T cells characterized by

expression of an invariant T cell receptor (TCR) Vα14-Jα18 chain, coupled preferentially to Vβ8·2,7 or -2 in mice or TCR Vα24-Jα18 and Vβ11 in humans [1]. NK T cells recognize glycolipids, rather than peptide antigens, presented by the major histocompatibility complex class I-like molecule CD1d. This results in rapid release of large amounts of T helper type 1 (Th1) [interferon (IFN)-γ] or Th2 [interleukin (IL)-4] cytokines, which in turn can activate dendritic cells, NK cells and B cells as well as conventional PLX4032 in vivo CD4+ and CD8+ T cells [2,3]. Thereby, NK T cells play a pivotal role as intermediates between the innate and the adaptive immune system and have the capacity to enhance host immunity to microbial infections and cancer as well as prevent autoimmunity [4–6]. In healthy individuals, the frequency of NK T cells in the peripheral blood is relatively low and ranges between 0·01% to 0·2% of total lymphocytes [7–9]. In cancer patients, NK T cell counts are reduced further compared to age- and gender-matched healthy controls [7,8] and usually defective in IFN-γ production upon stimulation [10,11]. Low circulating NK T cell numbers were found to predict poor clinical outcome in patients with Amobarbital head and neck cancer [12]. Attempts have been made

to stimulate NK T cell expansion with the glycolipid α-galactosylceramide (αGalCer) in order to stimulate anti-tumour responses in cancer patients [13–18]. In 10 of 17 non-small cell lung cancer patients this resulted in prolonged median survival time [19]. In an IFN-α trial of patients with metastatic renal cell carcinoma (RCC), a disease that has not been associated with high NK T cell numbers previously, we detected unusually high levels of circulating NK T cells in two of 14 patients. This prompted us to characterize these cells further to elucidate whether they were related to the therapy and had anti-tumour effectivity. All patients had primary metastatic RCC, patient B2 had clear cell RCC with sarcomatoid component and patient B7 had papillary RCC.