The Role of PD-1 in Skin Immunity and Implications for Cancer Treatments

Recent research from Weill Cornell Medicine has revealed a dual role for PD-1, a molecule traditionally known for dampening immune responses, in the formation of long-lasting skin immune defenses. The study demonstrates that PD-1 not only functions as an immune checkpoint but is also essential for guiding T cells to become resident memory cells (TRM) in the skin—cells that are critical for rapid defense against infections and potentially cancer. During infection, PD-1 acts as a key regulator, steering T cells to establish a protective presence in the skin. When PD-1 activity is blocked, either pharmacologically or genetically, the development and anchoring of these memory T cells are impaired, which could influence both the effectiveness of immune responses and the occurrence of side effects during immunotherapy.

The team found that PD-1 works synergistically with TGF-β, a cytokine involved in immune signaling, to promote TRM cell formation. Blocking PD-1 early in infection hampers the process, but adding TGF-β can rescue T cell development, underscoring the importance of timing in immune regulation. These findings challenge the current understanding of PD-1 solely as an immune suppressant and suggest that its role is more nuanced, actively supporting the development of immune memory in the skin.

Implications of this research are significant for cancer immunotherapy. PD-1 inhibitors, which are effective in treating cancers like melanoma, may inadvertently interfere with beneficial skin immune defenses if used prematurely or without consideration of timing. Furthermore, these insights could guide the development of more targeted therapies that maximize anti-cancer effects while minimizing adverse skin reactions and other side effects. The research highlights the importance of understanding immune cell memory formation to refine treatments for cancer and autoimmune diseases, promising new avenues for personalized medicine.

For additional information, consult the original study in Nature Immunology: [DOI: 10.1038/s41590-025-02228-1]. This research underscores the complex roles of immune checkpoints and the need to consider their timing and context in therapeutic strategies.

source: https://medicalxpress.com/news/2025-07-uncovering-immune-molecule-skin-defense.html