IFN-γ Approaches in Tumor Suppression, Its Challenges, and Future Directions: A Review of Recent Advances

IFN-gamma is recognized as an immunoregulatory cytokine due to its dual role in both accelerating and dampening immunological responses. Accordingly, in the context of tumor immunotherapy, the therapeutic outcome of IFN-gamma is contingent upon factors such as dosage and the expression status of downstream signaling molecules. Furthermore, the coadministration of IFN-gamma with various immunestimulatory agents, including anticheckpoint inhibitors, chemotherapeutic agents, and herbal-based medicines, may potentially overcome the IFN-gamma-related challenges and enhance the response rate. We decipher the mechanisms of tumor cell eradication facilitated by IFN-gamma, the last achievements in IFN-gamma-mediated tumor immunotherapy across various cancers, and the strategies to address the failure of IFN-gamma-based tumor immunotherapy. Unraveling the molecular mechanisms that lead to failure in IFN-gamma-based antitumor actions could assist in pinpointing therapeutic agents that target the immune-modulatory features of IFN-gamma, thereby increasing the antitumor response rate.