Albumin uptake through FcRn promotes tumor-associated macrophage maturation and albumin-bound immunotherapy response.

Tumor-associated macrophages (TAMs) are the main nonmalignant cells accumulating albumin in tumors, with FcRn-mediated uptake crucial for their maturation and immunotherapy response.

• Why it matters: Understanding how albumin influences TAM behavior is vital because TAMs play a key role in tumor progression and response to immunotherapy, yet their regulation by endogenous molecules remains unclear.
• What they did: The study used mouse models, bone marrow chimeras, and adoptive transfers to demonstrate that FcRn in myeloid cells drives albumin uptake and TAM maturation, with clinical data linking low albumin to fewer TAMs.
• The result: Albumin engagement activates p62-Nrf2 signaling, promoting TAM maturation; harnessing this pathway enhances immunotherapy efficacy, highlighting albumin’s role as an endogenous regulator of tumor immunity.