IFNα is a critical cytokine underpinning successful immunity. Individuals can produce up to 12 subtypes of these potent cytokines. The role of each subtype has not been investigated thoroughly and the potential of an individual subtype to favourably modulate an immune response is not well understood. A systematic evaluation of multiple subtypes was conducted by transducing the B16 murine melanoma cell line with five individual IFNα subtypes (B16_IFNα_2;4;5;6;9). Wildtype mice inoculated with B16_eGFP control cells establish a large single solid tumour mass after ∼3 weeks. In contrast, mice inoculated with B16_IFNα_4;5;6 showed a substantial delay in disease progression for a prolonged period of time before ultimately succumbing to their disease. Cohorts of mice challenged with B16_IFNα_2;9 had a slight delay in disease progression as compared to those injected with control B16_eGFP cells. Interestingly, not all animals receiving B16_IFNα_2;9 develop a tumour, with a significant proportion of animals appearing cancer free. 

B16_IFNα_2;4;5;6;9, tumours grew at the same rate as B16 control cells in IFNAR^o/o mice, indicating that all IFNα subtypes tested mediate their anti-tumour effects through the immune system. To investigate this further, RAG^o/o mice were inoculated with all cell lines. Tumour growth was restricted in RAG^o/o mice challenged with B16_IFNα_4;5;6, however, all mice ultimately succumbed to widespread metastatic disease in lymph nodes and major organs. A delay in disease progression was observed in RAG^o/o mice inoculated with B16_IFNα_2;9, but all mice ultimately developed large palpable masses. These results demonstrate that all the subtypes tested can favourably modulate aspects of innate immunity to provide enhanced control of an aggressive tumour. Interestingly, IFNα_4;5;6 enhances an adaptive immune response capable of limiting tumour dissemination. Furthermore, IFNα_2;9 can initiate an effective adaptive immune response capable of providing complete protection against tumour challenge.