Lymph node microenvironment rewires ferroptosis redox defenses.

Palma et al. show that melanoma cells adapt to oxidative stress imposed by the lymphatic niche by shifting their dependency from glutathione peroxidase 4 (GPX4) to ferroptosis suppressor protein 1 (FSP1), to protect from ferroptosis. This highlights the importance of the microenvironment in shaping ferroptosis defenses and supports FSP1 as a targetable vulnerability for lymph node metastases.