Commensal Papillomavirus Immunity Preserves the Homeostasis of Highly Mutated Normal Skin

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2024 Dec 13

PMID 39672169

Authors

Heehwa G Son

Dat Thinh Ha

Yun Xia

Tiancheng Li

Jasmine Blandin

Tomonori Oka

Marjan Azin

Danielle N Conrad

Can Zhou

Yuhan Zeng

Tatsuya Hasegawa

John D Strickley

Jonathan L Messerschmidt

Ranya Guennoun

Tal H Erlich

Gregory L Shoemaker

Luke H Johnson

Kenneth E Palmer

David E Fisher

Thomas D Horn

Victor A Neel

Rosalynn M Nazarian

Joongho J Joh

Shadmehr Demehri

Affiliations

Soon will be listed here.

Abstract

Immunosuppression commonly disrupts the homeostasis of mutated normal skin, leading to widespread skin dysplasia and field cancerization. However, the immune system's role in maintaining the normal state of mutated tissues remains uncertain. Herein, we demonstrate that T cell immunity to cutaneotropic papillomaviruses promotes the homeostasis of ultraviolet radiation-damaged skin. Mouse papillomavirus (MmuPV1) colonization blocks the expansion of mutant p53 clones in the epidermis in a CD8 T cell-dependent manner. MmuPV1 activity is increased in p53-deficient keratinocytes, leading to their specific targeting by CD8 T cells in the skin. Sun-exposed human skin containing mutant p53 clones shows increased epidermal beta-human papillomavirus (β-HPV) activity and CD8 T cell infiltrates compared with sun-protected skin. The expansion of mutant p53 clones in premalignant skin lesions associates with β-HPV loss. Thus, immunity to commensal HPVs contributes to the homeostasis of mutated normal skin, highlighting the role of virome-immune system interactions in preserving aging human tissues.

Citing Articles

Human Papillomavirus Vaccination and Actinic Keratosis Burden: The VAXAK Randomized Clinical Trial.

Wenande E, Hastrup A, Wiegell S, Philipsen P, Thomsen N, Demehri S JAMA Dermatol. 2025; .

PMID: 40047786 PMC: 11886873. DOI: 10.1001/jamadermatol.2025.0531.

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