Patients receiving a specific type of immunotherapy for lung cancer may get an added benefit from the treatment — darker hair. Researchers at Universitat Autònoma de Barcelona in Spain tracked the color of 14 patients’ hair before and during treatment with anti–programmed cell death 1 and anti–programmed cell death ligand 1 (anti-PD1 and anti–PD-L1, respectively) therapies. Thirteen patients had diffuse darkening of the hair, while one developed black patches between white hairs. This pigmentation could be used as a marker to determine whether patients receiving anti-PD1/anti–PD-L1 therapy for lung cancer are responding well to the treatment, the scientists suggest. The results were published in JAMA Dermatology.

“This is the first description of hair repigmentation during immunotherapy for lung cancer,” says Noelia Rivera, M.D., of Universitat Autònoma de Barcelona. She notes that the treatment can trigger hair depigmentation and skin depigmentation when used to treat malignant melanoma. “Using the same drug for a different disease—lung cancer —we could observe a completely opposed effect,” she says.

The findings are significant, Rivera explains, because even though knowledge of the immune system is opening new fields, there is still a lot to discover. After scouring journal articles, she and colleagues couldn’t identify a clear mechanism to explain why lung cancer patients treated with anti–programmed cell death 1 (anti–PD-1) and anti–programmed cell death ligand 1 (anti–PD-L1) therapies would grow darker hair, while patients treated for melanoma would lose color in their hair and skin. The results suggest that the same drug might turn different biological “keys” depending on the target of the immune system in different cancers.

The team came across the link between the anti–PD-1 and anti–PD-L1 therapies and hair repigmentation while monitoring patients for depigmentation of the skin and hair. The patients were treated with one of two anti–PD-1 drugs — nivolumab or pembrolizumab — or one anti–PD-L1— atezolizumab — drug, approved for treating metastatic non–small-cell lung cancer. The drugs work by blocking the programmed death receptor-1 and PD ligand-1, which are immune checkpoints. They prevent the immune system from attacking the patient’s own tissues. So, by blocking receptors, tumors can’t escape the immune system response.

Therefore, the immune system can attack melanoma or lung cancer cells. But there’s a caveat. Because of the way anti-PD-1 therapies work, they can also stimulate autoimmune diseases. Vitiligo is considered an autoimmune disorder, Rivera notes. Hair repigmentation, however, isn’t a disorder. So, understanding how the body generates darker hair during lung cancer treatment could offer clues to treating vitiligo or hair aging. “Research is required to find out the mechanisms of hair repigmentation before being able to harness this or any other molecule to treat vitiligo or hair aging,” Rivera notes.

Despite the ubiquity of graying hair with age, the roots of such depigmenation are unknown. Melanocytes are the cells where melanin, the pigment that gives skin, hair, and eyes its dark color, are stored. As we age, these pigment-harboring cells are shed from the skin, hair, and eyes. That may be a result of increased death of these cells, or a result of oxidative stress, studies suggest. The team noted in the paper that “gray hair follicles still preserve a reduced number of differentiated and functioning melanocytes located in the hair bulb. This reduced number of melanocytes may explain the possibility of hair repigmentation under appropriate conditions.”

Other researchers have observed hair repigmentation when patients were treated with drugs such as thalidomide, lenalidomide, erlotinib, adalimumab or etretinate. That’s led some scientists to conclude that hair repigmentation is a result of drugs blocking certain proinflammatory molecules, such as tumor necrosis factor-α and interleukin 1. These molecules can stifle the production of melanin, so inhibiting them might lead to repigmentation. But other researchers argue the opposite is true: hair-follicle melanocytes could be turned on by inflammatory molecules, leading to hair repigmentation after a targeted infection in the follicles.

Determining the exact mechanism that causes hair repigmentation will take time. In the meantime, Rivera and colleagues plan to continue to monitor the patients treated for lung cancer for adverse effects on their skin, such as loss of pigmentation. The team also wants to confirm that hair repigmentation could serve as a good prognosis marker in lung cancer patients.

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