This thesis establishes that distinct interferon alpha (IFNa) subtypes have different immunomodulatory roles against cancer. The IFNa family encompasses a group of cytokines that are critical for defending the host against pathogens and cancer. Whilst all members of the IFNa family signal through one receptor, the individual IFNa subtypes display varying biological potencies against viruses. Before this thesis, there was a paucity of information about the role and potential of distinct IFNa subtypes in controlling tumour growth. This thesis demonstrates that exploiting the distinct activities of a given IFNa subtype may have important ramifications for improving cancer immunotherapies.