Treatment of relapsing HPV diseases by restored function of natural killer cells

Andrea Lisco; Amy P. Hsu; Dimana Dimitrova; Diana M. Proctor; Emily M. Mace; Peiying Ye; Megan V. Anderson; Stephanie N. Hicks; Christopher Grivas; Dima A. Hammoud; Maura Manion; Gabriel J. Starrett; Alvin Farrel; Kerry Dobbs; Isaac Brownell; Christopher Buck; Luigi D. Notarangelo; Jordan S. Orange; Warren J. Leonard; Michael I. Orestes; Anju T. Peters; Jennifer A. Kanakry; Julia A. Segre; Heidi H. Kong; Irini Sereti

doi:10.1056/NEJMoa2102715

Treatment of relapsing HPV diseases by restored function of natural killer cells

Andrea Lisco^*, Amy P. Hsu, Dimana Dimitrova, Diana M. Proctor, Emily M. Mace, Peiying Ye, Megan V. Anderson, Stephanie N. Hicks, Christopher Grivas, Dima A. Hammoud, Maura Manion, Gabriel J. Starrett, Alvin Farrel, Kerry Dobbs, Isaac Brownell, Christopher Buck, Luigi D. Notarangelo, Jordan S. Orange, Warren J. Leonard, Michael I. OrestesAnju T. Peters, Jennifer A. Kanakry, Julia A. Segre, Heidi H. Kong, Irini Sereti

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.

Original language	English
Pages (from-to)	921-929
Number of pages	9
Journal	New England Journal of Medicine
Volume	385
Issue number	10
DOIs	https://doi.org/10.1056/NEJMoa2102715
State	Published - 2 Sep 2021
Externally published	Yes

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Lisco, A., Hsu, A. P., Dimitrova, D., Proctor, D. M., Mace, E. M., Ye, P., Anderson, M. V., Hicks, S. N., Grivas, C., Hammoud, D. A., Manion, M., Starrett, G. J., Farrel, A., Dobbs, K., Brownell, I., Buck, C., Notarangelo, L. D., Orange, J. S., Leonard, W. J., ... Sereti, I. (2021). Treatment of relapsing HPV diseases by restored function of natural killer cells. New England Journal of Medicine, 385(10), 921-929. https://doi.org/10.1056/NEJMoa2102715

@article{dee31745b99a413cb4132598ee2ba459,

title = "Treatment of relapsing HPV diseases by restored function of natural killer cells",

abstract = "Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.",

author = "Andrea Lisco and Hsu, {Amy P.} and Dimana Dimitrova and Proctor, {Diana M.} and Mace, {Emily M.} and Peiying Ye and Anderson, {Megan V.} and Hicks, {Stephanie N.} and Christopher Grivas and Hammoud, {Dima A.} and Maura Manion and Starrett, {Gabriel J.} and Alvin Farrel and Kerry Dobbs and Isaac Brownell and Christopher Buck and Notarangelo, {Luigi D.} and Orange, {Jordan S.} and Leonard, {Warren J.} and Orestes, {Michael I.} and Peters, {Anju T.} and Kanakry, {Jennifer A.} and Segre, {Julia A.} and Kong, {Heidi H.} and Irini Sereti",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Massachusetts Medical Society.",

year = "2021",

month = sep,

day = "2",

doi = "10.1056/NEJMoa2102715",

language = "English",

volume = "385",

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Lisco, A, Hsu, AP, Dimitrova, D, Proctor, DM, Mace, EM, Ye, P, Anderson, MV, Hicks, SN, Grivas, C, Hammoud, DA, Manion, M, Starrett, GJ, Farrel, A, Dobbs, K, Brownell, I, Buck, C, Notarangelo, LD, Orange, JS, Leonard, WJ, Orestes, MI, Peters, AT, Kanakry, JA, Segre, JA, Kong, HH & Sereti, I 2021, 'Treatment of relapsing HPV diseases by restored function of natural killer cells', New England Journal of Medicine, vol. 385, no. 10, pp. 921-929. https://doi.org/10.1056/NEJMoa2102715

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T1 - Treatment of relapsing HPV diseases by restored function of natural killer cells

AU - Lisco, Andrea

AU - Hsu, Amy P.

AU - Dimitrova, Dimana

AU - Proctor, Diana M.

AU - Mace, Emily M.

AU - Ye, Peiying

AU - Anderson, Megan V.

AU - Hicks, Stephanie N.

AU - Grivas, Christopher

AU - Hammoud, Dima A.

AU - Manion, Maura

AU - Starrett, Gabriel J.

AU - Farrel, Alvin

AU - Dobbs, Kerry

AU - Brownell, Isaac

AU - Buck, Christopher

AU - Notarangelo, Luigi D.

AU - Orange, Jordan S.

AU - Leonard, Warren J.

AU - Orestes, Michael I.

AU - Peters, Anju T.

AU - Kanakry, Jennifer A.

AU - Segre, Julia A.

AU - Kong, Heidi H.

AU - Sereti, Irini

PY - 2021/9/2

Y1 - 2021/9/2

N2 - Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.

AB - Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.

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VL - 385

SP - 921

EP - 929

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 10

ER -

Treatment of relapsing HPV diseases by restored function of natural killer cells

Abstract

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