Influence of T Cell Cytokines on Tumor-Immune Interactions in Brain Metastases

Recent research from Memorial Sloan Kettering Cancer Center has uncovered the critical role of T cell-derived cytokines, especially interferon-gamma (IFNγ), in modulating immune responses within the leptomeninges—the protective membranes enveloping the brain and spinal cord—during metastasis. The study demonstrates that IFNγ plays a pivotal role in orchestrating a network involving dendritic cells and natural killer (NK) cells, which collectively work to suppress tumor growth in the cerebrospinal fluid-filled spaces. These findings were derived from extensive experiments using syngeneic mouse models of lung, breast, and melanoma cancers, alongside analyses of human cerebrospinal fluid samples from patients with different cancers, with and without leptomeningeal metastases.

The researchers identified T cells as the primary source of IFNγ in the leptomeninges. Overexpressing IFNγ in mouse models reduced tumor burden effectively without apparent neurotoxicity. Proteogenomic analyses revealed that IFNγ promotes the maturation of conventional dendritic cells into migratory phenotypes that secrete cytokines such as IL-12 and IL-15, which further stimulate NK cell proliferation and cytotoxic activity. Notably, depleting NK cells or disrupting dendritic cell signaling pathways nullified the anti-tumor effects, indicating a critical immune circuit mediated by IFNγ.

This research highlights a promising therapeutic mechanism—activating the body's own immune signals to target and eliminate cancer cells within the central nervous system. As leptomeningeal metastasis remains a significant clinical challenge, these findings suggest that strategies enhancing IFNγ signaling or boosting dendritic and NK cell activity could open new avenues for treating metastatic brain cancer. If confirmed in human studies, harnessing this immune pathway could provide vital new options for patients suffering from advanced cancers such as breast, lung, and melanoma, potentially improving survival and disease management.

Source: https://medicalxpress.com/news/2025-05-cell-cytokines-tumor-immune-interactions.html