Shawn Demehri, MD, PhD

Heehwa Son, PhD

What alerts the immune system, especially T cells, to recognize and respond to damaged or altered cells within normal tissues?

In a new study led by Natalie Andresen of Harvard Medical School; Heehwa Son, PhD, and Shawn Demehri, MD, PhD, of Mass General Brigham Cancer Institute; and Joongho Joh, PhD, of the University of Louisville Health Sciences Center, scientists explored how T cells recognize and control groups of abnormal cells that arise in the top layer of skin as a consequence of sun exposure.

Through their experiments, they found that mouse skin exposed to UV light displayed more total DNA mutations than human facial skin exposed to sunlight. Because UV-exposed mouse skin had so many mutant cells, one theory was that the formation of new, “foreign” proteins (neoantigens) might draw T cells’ attention.

However, mice with and without papilloma virus had markedly different T cell responses despite similar mutation levels—suggesting mutations alone were not enough to alert T cells. Mice with the virus had significantly more CD8+ T cells, and when those T cells were depleted in infected mice, tumors increased significantly.

These findings suggest that viral antigens—rather than neoantigens alone—may act as an early “alarm,” helping T cells recognize mutated skin cells before they become cancerous. In other words, viruses that commonly live on the skin may help initiate immune surveillance of sun-damaged cells.

Published in JCI Insight on May 5, 2026 | Read the paper: “Virome antigens as triggers for immune recognition of mutant clones in normal tissues”

Summary reviewed by: Shawn Demehri, MD, PhD, senior author