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Modulation of human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and conventional anticancer therapies
1Department of Medicine, University of Queensland, Brisbane, Australia.
Abstract:
Immunotherapy strategies aimed at increasing human Valpha24(+)Vbeta11(+) natural killer T (NKT) cell numbers are currently a major focus. To provide further information towards the goal of NKT cell-based immunotherapy, we assessed the effects of age, cancer status and prior anticancer treatment on NKT cell numbers and their expansion capacity following alpha-galactosylceramide (alpha-GalCer) stimulation. The percentage and absolute number of peripheral blood NKT cells was assessed in 40 healthy donors and 109 solid cancer patients (colorectal (n=33), breast (n=10), melanoma (n=17), lung (n=8), renal cell carcinoma (n=10), other cancers (n=31)). Responsiveness to alpha-GalCer stimulation was also assessed in 28 of the cancer patients and 37 of the healthy donors. Natural killer T cell numbers were significantly reduced in melanoma and breast cancer patients. While NKT numbers decreased with age in healthy donors, NKT cells were decreased in these cancer subgroups despite age and sex adjustments. Prior radiation treatment was shown to contribute to the observed reduction in melanoma patients. Although cancer patient NKT cells were significantly less responsive to alpha-GalCer stimulation, they remained capable of substantial expansion. Natural killer T cells are therefore modulated by age, malignancy and prior anticancer treatment; however, cancer patient NKT cells remain capable of responding to alpha-GalCer-based immenotherapies.
Insights
Immunotherapy targeting natural killer T (NKT) cells is promising. This study found that cancer and prior treatments reduce NKT cell numbers, but they can still expand in response to alpha-galactosylceramide (alpha-GalCer) therapy.
Area of Science:
- Immunology
- Cancer Research
- Immunotherapy
Background:
- Natural killer T (NKT) cells are crucial immune cells targeted for immunotherapy.
- Understanding factors affecting NKT cell numbers and function is vital for developing effective NKT cell-based therapies.
Purpose of the Study:
- To investigate the impact of age, cancer status, and prior anticancer treatments on peripheral blood NKT cell numbers and their expansion capacity.
- To evaluate the responsiveness of NKT cells from cancer patients to alpha-galactosylceramide (alpha-GalCer) stimulation.
Main Methods:
- Assessed NKT cell percentage and absolute numbers in 40 healthy donors and 109 solid cancer patients.
- Analyzed NKT cell responsiveness to alpha-GalCer stimulation in a subset of patients and healthy donors.
- Correlated NKT cell levels with age, cancer type, and prior treatments like radiation.
Main Results:
- NKT cell numbers were significantly reduced in melanoma and breast cancer patients.
- NKT cell numbers decreased with age in healthy donors and were lower in cancer patients irrespective of age and sex.
- Prior radiation treatment was linked to reduced NKT cells in melanoma patients.
- Cancer patient NKT cells showed reduced responsiveness but retained significant expansion capacity after alpha-GalCer stimulation.
Conclusions:
- NKT cell numbers are modulated by age, malignancy, and prior anticancer treatments.
- Despite reductions, NKT cells in cancer patients remain capable of responding to alpha-GalCer-based immunotherapies, suggesting potential therapeutic utility.
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