The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Abstract

Background: Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.

Methods: The number, IFN-gamma production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.

Results: The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-gamma production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.

Conclusion: NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.

Fig. 1

NKT cells in the peripheral blood of healthy control subjects and patients before radiotherapy. No significant differences were observed in the number of NKT cells between the patients and the control subjects

Fig. 2

a The number of CD3-positive T cells is shown. The number of T cells was significantly decreased after irradiation. b The number of NKT cells is shown. NKT cells did not decrease significantly in number

Fig. 3

The expansion capacity of NKT cells in cancer patients in response to α-GalCer and IL-2 is shown. NKT cells collected after and before radiation therapy proliferated

Fig. 4

a The IFN-γ spots induced by α-GalCer-pulsed DCs from fresh isolated PBMCs are shown. These spots decreased significantly after radiation therapy compared with those before therapy. b After culture for 7 days with α-GalCer and IL-2, the IFN-γ spots reflected by α-GalCer-pulsed DCs are shown. Those spots were significantly increased after radiation therapy

Fig. 5

The cytotoxic activity of NKT cells is shown. The target cells were K562 and U937. The E:T ratios were 16:1, 8:1, 4:1, 2:1 and 1:1. Effector cells from pre-radiation and post-radiation are represented by open circles and closed boxes, respectively