Home Medizin Es wurde festgestellt, dass das Ziel eines Immun-Checkpoint-Inhibitors das Wachstum von Hautkrebs fördert

Es wurde festgestellt, dass das Ziel eines Immun-Checkpoint-Inhibitors das Wachstum von Hautkrebs fördert

von NFI Redaktion


The programmed cell death 1 (PD-1) is an important target for immune checkpoint inhibitor therapies, which block its signaling and enhance T cell activity. PD-1 inhibitors are approved for the treatment of various types of cancer.

However, the functions of PD-1 can vary depending on the cell and cancer type, and can either promote or suppress the progression of the disease. Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer, responds well to immune checkpoint inhibitor therapy. However, it was not previously known whether MCC cells themselves express PD-1, and it was unclear exactly how cancer cell-intrinsic PD-1 contributes to tumor growth.

A study conducted by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham health system, identified a new mechanism by which PD-1 promotes the progression of MCC. Through a series of experiments, the researchers demonstrated PD-1 expression on MCC cells in preclinical models and tumor samples from patients. They found that the binding of MCC PD-1 receptor to its ligands accelerated tumor growth by activating the mammalian target of rapamycin (mTOR) pathway and generating mitochondrial reactive oxygen species (mtROS) to promote MCC growth.

Subsequently, the authors showed that inhibiting mTOR signaling and neutralizing mtROS suppressed MCC PD-1-mediated tumor proliferation in mice. They suggest that these findings could help in the development of new treatments to stop the progression of MCC even in patients without T cell immunity.

For the first time, our work identifies PD-1 as an MCC intrinsic receptor that promotes tumor growth through downstream mTOR signals and production of reactive oxygen species in the mitochondria. Targeting this tumor-intrinsic PD-1 signaling network could help optimize immune checkpoint therapy regimens and improve treatment outcomes for MCC patients.


Tobias Schatton, PharmD, PhD, corresponding author of the Department of Dermatology, Brigham and Women’s Hospital

Source:

Brigham and Women’s Hospital

Journal reference:

Martins, C., et al. (2024) Tumor-intrinsic PD-1 promotes the growth of Merkel cell carcinomas by activating downstream mTOR-mitochondrial ROS signaling. Science Advances. doi.org/10.1126/sciadv.adi2012.

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