IL-34 promotes differentiation and survival of immunosuppressive macrophages within the tumor microenvironment, potentially reducing T-cell–mediated antitumor activity. This study evaluated the effects of IL-34 blockade and IL-34 knockout in SPCcre KrasG12D murine lung tumors. Mice treated with anti-IL-34 antibodies displayed increased CD3⁺ and CD8⁺ T-cell infiltration and reduced F4/80⁺ macrophage density relative to controls, indicating a shift toward a more immunogenic microenvironment. IL-34 knockout mice exhibited reduced macrophage staining but less pronounced changes compared to antibody-treated animals, suggesting alternative compensatory pathways. These results support the role of IL-34 in fostering macrophage-driven immune suppression and highlight its potential as a therapeutic target complementing PI3Kγ-mediated immunomodulation. Findings align with prior studies showing synergy between myeloid-directed therapies and T-cell–based immunotherapies.