Interferon-α enhances NK cell function to counteract autologous platelet-mediated tumor immune evasion.

BACKGROUND

Natural Killer (NK) cells, a cellular defense component of the innate immune system, play a vital role in anti-tumor immunity. As interest in NK cell-based therapies grows within the field of cancer treatment, assessing potential negative interferences and adverse interactions is essential. Although platelets are recognized as modulators of tumor immunity, the impact of autologous platelets on NK cell function remains insufficiently explored in the realm of personalized medicine.

METHODS

To investigate the role of autologous platelets in modulating NK cell activity, we developed a novel assessment platform using fresh blood samples from 34 healthy donors (25 females, 9 males; mean age 28.29 ± 6.25 years). NK cells, with or without prior IFN-α stimulation, were co-cultured with K562 leukemia cells in the presence or absence of autologous platelets to assess functional responses.

RESULTS

NK cells can exert anti-tumor immunity by releasing cytokines like IFN-γ and directly eliminating tumor cells through cytotoxic granules. In our co-culture system, platelets demonstrated suppressive effects on NK cell IFN-γ production and cytotoxic degranulation, resulting in impaired tumor cell killing. Notably, this suppression was effectively reversed by IFN-α treatment, which restored NK cell cytotoxic function and cytokine responses in all donors tested.

CONCLUSION

Our study reveals that autologous platelets compromise NK cell-mediated anti-tumor responses, but this suppression can be overcome with IFN-α treatment. The assessment platform we introduced provides a practical tool to study platelet–NK–tumor interactions and serves as a valuable model for screening immunomodulatory agents and tailoring NK cell-based therapies.