Cargando…
Immunity to Commensal Papillomaviruses protects against Skin Cancer
Immunosuppression increases the risk of cancers associated with viral infection(1). In particular, squamous cell carcinoma (SCC) of the skin has a >100-fold increased risk in immunosuppressed patients and has been associated with beta human papillomavirus (β-HPV) infection(2–4). Previous studies,...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872936/ https://www.ncbi.nlm.nih.gov/pubmed/31666702 http://dx.doi.org/10.1038/s41586-019-1719-9 |
_version_ | 1783472594741100544 |
---|---|
author | Strickley, John D. Messerschmidt, Jonathan L. Awad, Mary E. Li, Tiancheng Hasegawa, Tatsuya Ha, Dat Thinh Nabeta, Henry W. Bevins, Paul A. Ngo, Kenneth H. Asgari, Maryam M. Nazarian, Rosalynn M. Neel, Victor A. Jenson, Alfred Bennett Joh, Joongho Demehri, Shadmehr |
author_facet | Strickley, John D. Messerschmidt, Jonathan L. Awad, Mary E. Li, Tiancheng Hasegawa, Tatsuya Ha, Dat Thinh Nabeta, Henry W. Bevins, Paul A. Ngo, Kenneth H. Asgari, Maryam M. Nazarian, Rosalynn M. Neel, Victor A. Jenson, Alfred Bennett Joh, Joongho Demehri, Shadmehr |
author_sort | Strickley, John D. |
collection | PubMed |
description | Immunosuppression increases the risk of cancers associated with viral infection(1). In particular, squamous cell carcinoma (SCC) of the skin has a >100-fold increased risk in immunosuppressed patients and has been associated with beta human papillomavirus (β-HPV) infection(2–4). Previous studies, however, have failed to establish a causative role for HPVs in driving skin cancer development. Herein, we provide an alternative explanation for this association by demonstrating that the T cell immunity against commensal papillomaviruses suppresses skin cancer in immunocompetent hosts. The loss of this immunity, rather than the oncogenic effect of HPVs, is the reason for the markedly increased risk of skin cancer in immunosuppressed patients. To investigate the impact of papillomavirus on carcinogen-driven skin cancer, we colonized several strains of immunocompetent mice with mouse papillomavirus type 1 (MmuPV1)(5). Mice with natural anti-MmuPV1 immunity after colonization and acquired immunity due to T cell transfer from immune mice or MmuPV1 vaccination were protected against chemical- and ultraviolet (UV)-induced skin carcinogenesis in a CD8(+) T cell-dependent manner. RNA and DNA in situ hybridizations for 25 commensal β-HPVs revealed a significant reduction in viral activity and load in human skin cancer compared to the adjacent normal skin, suggesting a strong immune selection against virus-positive malignant cells. Consistently, β-HPV E7 peptides activated CD8(+) T cells from normal human skin. Our findings reveal a beneficial role for commensal viruses and establish the foundation for novel immune-based approaches to block skin cancer development by boosting immunity against the commensal HPVs present in all of our skin. |
format | Online Article Text |
id | pubmed-6872936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68729362020-04-30 Immunity to Commensal Papillomaviruses protects against Skin Cancer Strickley, John D. Messerschmidt, Jonathan L. Awad, Mary E. Li, Tiancheng Hasegawa, Tatsuya Ha, Dat Thinh Nabeta, Henry W. Bevins, Paul A. Ngo, Kenneth H. Asgari, Maryam M. Nazarian, Rosalynn M. Neel, Victor A. Jenson, Alfred Bennett Joh, Joongho Demehri, Shadmehr Nature Article Immunosuppression increases the risk of cancers associated with viral infection(1). In particular, squamous cell carcinoma (SCC) of the skin has a >100-fold increased risk in immunosuppressed patients and has been associated with beta human papillomavirus (β-HPV) infection(2–4). Previous studies, however, have failed to establish a causative role for HPVs in driving skin cancer development. Herein, we provide an alternative explanation for this association by demonstrating that the T cell immunity against commensal papillomaviruses suppresses skin cancer in immunocompetent hosts. The loss of this immunity, rather than the oncogenic effect of HPVs, is the reason for the markedly increased risk of skin cancer in immunosuppressed patients. To investigate the impact of papillomavirus on carcinogen-driven skin cancer, we colonized several strains of immunocompetent mice with mouse papillomavirus type 1 (MmuPV1)(5). Mice with natural anti-MmuPV1 immunity after colonization and acquired immunity due to T cell transfer from immune mice or MmuPV1 vaccination were protected against chemical- and ultraviolet (UV)-induced skin carcinogenesis in a CD8(+) T cell-dependent manner. RNA and DNA in situ hybridizations for 25 commensal β-HPVs revealed a significant reduction in viral activity and load in human skin cancer compared to the adjacent normal skin, suggesting a strong immune selection against virus-positive malignant cells. Consistently, β-HPV E7 peptides activated CD8(+) T cells from normal human skin. Our findings reveal a beneficial role for commensal viruses and establish the foundation for novel immune-based approaches to block skin cancer development by boosting immunity against the commensal HPVs present in all of our skin. 2019-10-30 2019-11 /pmc/articles/PMC6872936/ /pubmed/31666702 http://dx.doi.org/10.1038/s41586-019-1719-9 Text en Reprint and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) . Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Strickley, John D. Messerschmidt, Jonathan L. Awad, Mary E. Li, Tiancheng Hasegawa, Tatsuya Ha, Dat Thinh Nabeta, Henry W. Bevins, Paul A. Ngo, Kenneth H. Asgari, Maryam M. Nazarian, Rosalynn M. Neel, Victor A. Jenson, Alfred Bennett Joh, Joongho Demehri, Shadmehr Immunity to Commensal Papillomaviruses protects against Skin Cancer |
title | Immunity to Commensal Papillomaviruses protects against Skin
Cancer |
title_full | Immunity to Commensal Papillomaviruses protects against Skin
Cancer |
title_fullStr | Immunity to Commensal Papillomaviruses protects against Skin
Cancer |
title_full_unstemmed | Immunity to Commensal Papillomaviruses protects against Skin
Cancer |
title_short | Immunity to Commensal Papillomaviruses protects against Skin
Cancer |
title_sort | immunity to commensal papillomaviruses protects against skin
cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872936/ https://www.ncbi.nlm.nih.gov/pubmed/31666702 http://dx.doi.org/10.1038/s41586-019-1719-9 |
work_keys_str_mv | AT strickleyjohnd immunitytocommensalpapillomavirusesprotectsagainstskincancer AT messerschmidtjonathanl immunitytocommensalpapillomavirusesprotectsagainstskincancer AT awadmarye immunitytocommensalpapillomavirusesprotectsagainstskincancer AT litiancheng immunitytocommensalpapillomavirusesprotectsagainstskincancer AT hasegawatatsuya immunitytocommensalpapillomavirusesprotectsagainstskincancer AT hadatthinh immunitytocommensalpapillomavirusesprotectsagainstskincancer AT nabetahenryw immunitytocommensalpapillomavirusesprotectsagainstskincancer AT bevinspaula immunitytocommensalpapillomavirusesprotectsagainstskincancer AT ngokennethh immunitytocommensalpapillomavirusesprotectsagainstskincancer AT asgarimaryamm immunitytocommensalpapillomavirusesprotectsagainstskincancer AT nazarianrosalynnm immunitytocommensalpapillomavirusesprotectsagainstskincancer AT neelvictora immunitytocommensalpapillomavirusesprotectsagainstskincancer AT jensonalfredbennett immunitytocommensalpapillomavirusesprotectsagainstskincancer AT johjoongho immunitytocommensalpapillomavirusesprotectsagainstskincancer AT demehrishadmehr immunitytocommensalpapillomavirusesprotectsagainstskincancer |