Inflammation is a reaction to harmful stimuli such as infection and tissue damage. It can be acute or chronic. In cancer, acute inflammation is protective, while chronic inflammation promotes tumors. Cytokines regulate inflammation by facilitating cell-cell communication. They can be pro-inflammatory or anti-inflammatory. Notably, the same cytokine, such as interleukin-1 (IL-1), can have either anti-tumoral or pro-tumoral effects depending on context, reflecting cytokines' dual nature in tumorigenesis. Cells release cytokines through various mechanisms, including gasdermin D (GSDMD), which creates membrane pores for IL-1β and IL-18 release. While both cytokines' roles are well understood, GSDMD’s involvement in tumor development remains unclear. This thesis investigated GSDMD’s role in tumor development, developed a targeted nanoparticle delivery system to improve a GSDMD inhibitor’s pharmacokinetics, and created a tumor-responsive immunocytokine for cancer treatment. The first project demonstrated that GSDMD is elevated in various human cancers. Our findings reveal a positive correlation between GSDMD expression and survival in breast cancer, contrasting with the lack of correlation in liver cancer. Moreover, GSDMD upregulation was associated with immune infiltration in breast cancer but not in liver cancer. However, GSDMD deficiency had no significant effect on tumor growth or immune response in mouse breast cancer and hepatoma models, suggesting that its role varies by tumor type and species. Additionally, the absence of GSDMD did not affect in vitro and in vivo immune responses upon Toll-like receptor stimulation, highlighting species-specific differences and the need for further research on GSDMD's anti-tumor effects. The second project developed a nanoparticle (NP) system to passively target phagocytic cells and deliver the GSDMD inhibitor necrosulfonamide (NSA). Three NP types with high drug-loading capacities were tested: mesoporous silica, porous crosslinked cyclodextrin carriers (CD), and mesoporous magnesium-phosphate carriers. Live-cell microscopy confirmed rapid NP uptake and effective NSA delivery to phagocytic cells. NSA-loaded NPs suppressed IL-1β secretion from primary murine and human macrophages in a concentration-dependent manner. CD NPs exhibited the strongest suppression in human macrophages, highlighting porous NPs' potential in delivering hydrophobic drugs to modulate inflammation. The third project developed a targeted immunocytokine by fusing a human epidermal growth factor receptor (HER2)-targeting antibody with a silenced interferon (IFN)-γ through a protease-sensitive linker to activate anti-tumoral immune responses locally. Analysis of protease expression across cancer types in the TCGA tumor database identified matrix metalloproteinase (MMP) 9 as a candidate for linker cleavage. The designed anti-HER2 MMP9-cleavable IFN-γ fusion protein specifically bound HER2-positive breast cancer cells in vitro. The fused IFN-γ was significantly attenuated but restored upon MMP9 cleavage, suggesting this fusion might reduce systemic side effects while retaining therapeutic efficacy in the tumor microenvironment. Stability studies in murine and human serum supported its feasibility, though additional in vivo studies are needed to assess efficacy. In conclusion, this thesis explored inflammation’s complex role in cancer, highlighting cytokines' multifaceted impact on tumor progression.