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Микробиом кожи у онкологических пациентов при зуде и других кожных токсических реакциях на фоне противоопухолевой терапии
Микробиом кожи у онкологических пациентов при зуде и других кожных токсических реакциях на фоне противоопухолевой терапии
Полонская А.С., Миченко А.В., Круглова Л.С., Шатохина Е.А., Львов А.Н. Микробиом кожи у онкологических пациентов при зуде и других кожных токсических реакциях на фоне противоопухолевой терапии. Consilium Medicum. 2023;25(6):400–405. DOI: 10.26442/20751753.2023.6.202302
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
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Аннотация
Современная противоопухолевая терапия характеризуется новыми таргетными и иммунотерапевтическими методами лечения, специфически воздействующими на мишени, экспрессирующиеся в опухолях. Однако многие из этих мишеней экспрессируются также и в постоянно пролиферирующем эпидермисе кожного покрова, что приводит к нарушению пролиферации и дифференциации кератиноцитов, развитию воспалительных реакций, снижению защитных функций кожи, нарушению синтеза антимикробных пептидов и развитию ряда кожных токсических реакций. В статье представлен обзор современных данных о нарушениях микробиома, сопровождающих развитие кожных токсических реакций. Рассмотрены потенциальные механизмы реализации влияния изменения микробиома кожи на формирование и поддержание высыпаний, формирующихся на фоне противоопухолевой терапии.
Ключевые слова: микробиом кожи, кожные токсические реакции, кожная токсичность, новообразования кожи, актинический кератоз, плоскоклеточный рак, лимфома
Keywords: skin microbiome, skin toxicity, toxic skin reactions, skin neoplasms, actinic keratosis, squamous cell carcinoma, lymphoma
Ключевые слова: микробиом кожи, кожные токсические реакции, кожная токсичность, новообразования кожи, актинический кератоз, плоскоклеточный рак, лимфома
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Keywords: skin microbiome, skin toxicity, toxic skin reactions, skin neoplasms, actinic keratosis, squamous cell carcinoma, lymphoma
Полный текст
Список литературы
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16. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. DOI:10.1126/science.aan4236
17. Полонская А.С., Шатохина Е.А., Круглова Л.С. Дерматологические нежелательные явления ингибиторов рецептора эпидермального фактора роста: современный взгляд на междисциплинарную проблему. Опухоли головы и шеи. 2021;11(4):97-109 [Polonskaia AS, Shatokhina EA, Kruglova LS. Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem. Head and Neck Tumors (HNT). 2021;11(4):97-109 (in Russian)].
DOI:10.17650/2222-1468-2021-11-4-97-109
18. Миченко А.В., Круглова Л.С., Шатохина Е.А., и др. Дерматологическая токсичность ингибиторов EGFR: патогенетическое обоснование и алгоритм коррекции акнеподобной сыпи. Онкогематология. 2021;16(4):50-8 [Michenko AV, Kruglova LS, Shatokhina EA. Dermatological toxicity of EGFR inhibitors: pathogenetic rationale and an algorithm for acne-like rash correction. Onkogematolog iya = Oncohematology. 2021;16(4):50-8 (in Russian)]. DOI:10.17650/1818-8346-2021-16-4-50-58
19. Ommori R, Nakamura Y, Miyagawa F, et al. Reduced induction of human β-defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies. Clin Exp Dermatol. 2020;45(8):1055-8. DOI:10.1111/ced.14311
20. Jia Z, Bao K, Wei P, et al. EGFR activation-induced decreases in claudin1 promote MUC5AC expression and exacerbate asthma in mice. Mucosal Immunol. 2021;14(1):125-34. DOI:10.1038/s41385-020-0272-z
21. Gerber PA, Kukova G, Buhren BA, Homey B. Density of Demodex folliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology. 2011;222(2):144-7. DOI:10.1159/000323001
22. Ramadan M, Hetta HF, Saleh MM, et al. Alterations in skin microbiome mediated by radiotherapy and their potential roles in the prognosis of radiotherapy-induced dermatitis: a pilot study. Sci Rep. 2021;11(1):5179. DOI:10.1038/s41598-021-84529-7
23. Zhang M, Jiang Z, Li D, et al. Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing. Microb Ecol. 2015;69(2):415-21.
DOI:10.1007/s0024 8-014-0504-4
24. Briaud P, Bastien S, Camus L, et al. Impact of coexistence phenotype between Staphylococcus aureus and Pseudomonas aeruginosa isolates on clinical outcomes among cystic fibrosis patients. Front Cell Infect Microbiol. 2020;10:266. DOI:10.3389/fcimb.2020.00266
25. Armbruster CR, Wolter DJ, Mishra M, et al. Staphylococcus aureus Protein A mediates interspecies interactions at the cell surface of Pseudomonas aeruginosa. mBio. 2016;7(3):e00538-16. DOI:10.1128/mBio.00538-16
2. Costello EK, Lauber CL, Hamady M, et al. Bacterial community variation in human body habitats across space and time. Science. 2009;326(5960):1694-7. DOI:10.1126/science.1177486
3. Nakatsuji T, Chiang HI, Jiang SB, et al. The microbiome extends to subepidermal compartments of normal skin. Nat Commun. 2013;4:1431. DOI:10.1038/ncomms2441
4. Khlebnikova AN, Petrunin DD. Physiological and pathogenic role of cutaneous microbiota. Treatment algorithms of secondary infected dermatoses. Consilium Medicum. Dermatology (Suppl.). 2016;4:18-25 (in Russian).
5. Murashkin NN, Epishev RV, Ivanov RA, et al. Innovations in Therapeutic Improvement of the Cutaneous Microbiome in Children with Atopic Dermatitis. Current Pediatrics. 2022;21(5):352-61 (in Russian). DOI:10.15690/vsp.v21i5.2449
6. Woo YR, Cho SH, Lee JD, Kim HS. The Human Microbiota and Skin Cancer. Int J Mol Sci. 2022;23(3):1813. DOI:10.3390/ijms23031813
7. Kehrmann J, Koch F, Zumdick S, et al. Reduced Staphylococcus Abundance Characterizes the Lesional Microbiome of Actinic Keratosis Patients after Field-Directed Therapies. Microbiol Spectr. 2023;11(3):e0440122. DOI:10.1128/spectrum.04401-22
8. Kullander J, Forslund O, Dillner J. Staphylococcus aureus and squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev. 2009;18(2):472-8.
DOI:10.1158/1055-9965.EPI-08-0905
9. Wood DLA, Lachner N, Tan JM, et al. A natural history of actinic keratosis and cutaneous squamous cell carcinoma microbiomes. mBio. 2018;9(5):e01432-18. DOI:10.1128/mBio.01432-18
10. Madhusudhan N, Pausan MR, Halwachs B, et al. Molecular profiling of keratinocyte skin tumors links Staphylococcus aureus overabundance and increased human b-defensin-2 expression to growth promotion of squamous cell carcinoma. Cancers (Basel). 2020;12(3):541. DOI:10.3390/cancers12030541
11. Molina-García M, Malvehy J, Granger C, et al. Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen's Disease and Squamous Cell Carcinoma: A Proposal. Dermatol Ther (Heidelb). 2022;12(2):361-80. DOI:10.1007/s13555-021-00644-3
12. Olisova OYu, Grabovskaya OV, Tetushkina IN, Kosoukhova OA. T-cell cutaneous lymphoma: diagnostic difficulties. Russian journal of skin and venereal diseases. 2013;3:4-6 (in Russian).
13. Salava A, Deptula P, Lyyski A, et al. Skin Microbiome in Cutaneous T-Cell Lymphoma by 16S and Whole-Genome Shotgun Sequencing. J Invest Dermatol. 2020;140(11):2304-8.e7. DOI:10.1016/j.jid.2020.03.951
14. Harkins CP, MacGibeny MA, Thompson K, et al. Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls. J Invest Dermatol. 2021;141(6):1604-8. DOI:10.1016/j.jid.2020.10.021
15. Mrázek J, Mekadim C, Kučerová P, et al. Melanoma-related changes in skin microbiome. Folia Microbiol (Praha). 2019;64(3):435-42. DOI:10.1007/s12223-018-00670-3
16. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. DOI:10.1126/science.aan4236
17. Polonskaia AS, Shatokhina EA, Kruglova LS. Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem. Head and Neck Tumors (HNT). 2021;11(4):97-109 (in Russian). DOI:10.17650/2222-1468-2021-11-4-97-109
18. Michenko AV, Kruglova LS, Shatokhina EA. Dermatological toxicity of EGFR inhibitors: pathogenetic rationale and an algorithm for acne-like rash correction. Onkogematolog iya = Oncohematology. 2021;16(4):50-8 (in Russian). DOI:10.17650/1818-8346-2021-16-4-50-58
19. Ommori R, Nakamura Y, Miyagawa F, et al. Reduced induction of human β-defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies. Clin Exp Dermatol. 2020;45(8):1055-8. DOI:10.1111/ced.14311
20. Jia Z, Bao K, Wei P, et al. EGFR activation-induced decreases in claudin1 promote MUC5AC expression and exacerbate asthma in mice. Mucosal Immunol. 2021;14(1):125-34. DOI:10.1038/s41385-020-0272-z
21. Gerber PA, Kukova G, Buhren BA, Homey B. Density of Demodex folliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology. 2011;222(2):144-7. DOI:10.1159/000323001
22. Ramadan M, Hetta HF, Saleh MM, et al. Alterations in skin microbiome mediated by radiotherapy and their potential roles in the prognosis of radiotherapy-induced dermatitis: a pilot study. Sci Rep. 2021;11(1):5179. DOI:10.1038/s41598-021-84529-7
23. Zhang M, Jiang Z, Li D, et al. Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing. Microb Ecol. 2015;69(2):415-21.
DOI:10.1007/s0024 8-014-0504-4
24. Briaud P, Bastien S, Camus L, et al. Impact of coexistence phenotype between Staphylococcus aureus and Pseudomonas aeruginosa isolates on clinical outcomes among cystic fibrosis patients. Front Cell Infect Microbiol. 2020;10:266. DOI:10.3389/fcimb.2020.00266
25. Armbruster CR, Wolter DJ, Mishra M, et al. Staphylococcus aureus Protein A mediates interspecies interactions at the cell surface of Pseudomonas aeruginosa. mBio. 2016;7(3):e00538-16. DOI:10.1128/mBio.00538-16
2. Costello EK, Lauber CL, Hamady M, et al. Bacterial community variation in human body habitats across space and time. Science. 2009;326(5960):1694-7. DOI:10.1126/science.1177486
3. Nakatsuji T, Chiang HI, Jiang SB, et al. The microbiome extends to subepidermal compartments of normal skin. Nat Commun. 2013;4:1431. DOI:10.1038/ncomms2441
4. Хлебникова А.Н., Петрунин Д.Д. Физиологическая и патогенетическая роль кожной микробиоты. Алгоритмы лечения дерматозов, осложненных вторичным инфицированием. Consilium Medicum. Дерматология (Прил.). 2016;4:18-25 [Khlebnikova AN, Petrunin DD. Physiological and pathogenic role of cutaneous microbiota. Treatment algorithms of secondary infected dermatoses. Consilium Medicum. Dermatology (Suppl.). 2016;4:18-25 (in Russian)].
5. Мурашкин Н.Н., Епишев Р.В., Иванов Р.А., и др. Инновации в терапевтической коррекции микробиома кожи при атопическом дерматите в детском возрасте. Вопросы современной педиатрии. 2022;21(5):352-61 [Murashkin NN, Epishev RV, Ivanov RA, et al. Innovations in Therapeutic Improvement of the Cutaneous Microbiome in Children with Atopic Dermatitis. Current Pediatrics. 2022;21(5):352-61 (in Russian)]. DOI:10.15690/vsp.v21i5.2449
6. Woo YR, Cho SH, Lee JD, Kim HS. The Human Microbiota and Skin Cancer. Int J Mol Sci. 2022;23(3):1813. DOI:10.3390/ijms23031813
7. Kehrmann J, Koch F, Zumdick S, et al. Reduced Staphylococcus Abundance Characterizes the Lesional Microbiome of Actinic Keratosis Patients after Field-Directed Therapies. Microbiol Spectr. 2023;11(3):e0440122. DOI:10.1128/spectrum.04401-22
8. Kullander J, Forslund O, Dillner J. Staphylococcus aureus and squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev. 2009;18(2):472-8.
DOI:10.1158/1055-9965.EPI-08-0905
9. Wood DLA, Lachner N, Tan JM, et al. A natural history of actinic keratosis and cutaneous squamous cell carcinoma microbiomes. mBio. 2018;9(5):e01432-18. DOI:10.1128/mBio.01432-18
10. Madhusudhan N, Pausan MR, Halwachs B, et al. Molecular profiling of keratinocyte skin tumors links Staphylococcus aureus overabundance and increased human b-defensin-2 expression to growth promotion of squamous cell carcinoma. Cancers (Basel). 2020;12(3):541. DOI:10.3390/cancers12030541
11. Molina-García M, Malvehy J, Granger C, et al. Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen's Disease and Squamous Cell Carcinoma: A Proposal. Dermatol Ther (Heidelb). 2022;12(2):361-80. DOI:10.1007/s13555-021-00644-3
12. Олисова О.Ю., Грабовская О.В., Тетушкина И.Н., Косоухова О.А. Т-клеточная лимфома кожи: трудности диагностики. Российский журнал кожных и венерических болезней. 2013;3:4-6 [Olisova OYu, Grabovskaya OV, Tetushkina IN, Kosoukhova OA. T-cell cutaneous lymphoma: diagnostic difficulties. Russian journal of skin and venereal diseases. 2013;3:4-6 (in Russian)].
13. Salava A, Deptula P, Lyyski A, et al. Skin Microbiome in Cutaneous T-Cell Lymphoma by 16S and Whole-Genome Shotgun Sequencing. J Invest Dermatol. 2020;140(11):2304-8.e7. DOI:10.1016/j.jid.2020.03.951
14. Harkins CP, MacGibeny MA, Thompson K, et al. Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls. J Invest Dermatol. 2021;141(6):1604-8. DOI:10.1016/j.jid.2020.10.021
15. Mrázek J, Mekadim C, Kučerová P, et al. Melanoma-related changes in skin microbiome. Folia Microbiol (Praha). 2019;64(3):435-42. DOI:10.1007/s12223-018-00670-3
16. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. DOI:10.1126/science.aan4236
17. Полонская А.С., Шатохина Е.А., Круглова Л.С. Дерматологические нежелательные явления ингибиторов рецептора эпидермального фактора роста: современный взгляд на междисциплинарную проблему. Опухоли головы и шеи. 2021;11(4):97-109 [Polonskaia AS, Shatokhina EA, Kruglova LS. Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem. Head and Neck Tumors (HNT). 2021;11(4):97-109 (in Russian)].
DOI:10.17650/2222-1468-2021-11-4-97-109
18. Миченко А.В., Круглова Л.С., Шатохина Е.А., и др. Дерматологическая токсичность ингибиторов EGFR: патогенетическое обоснование и алгоритм коррекции акнеподобной сыпи. Онкогематология. 2021;16(4):50-8 [Michenko AV, Kruglova LS, Shatokhina EA. Dermatological toxicity of EGFR inhibitors: pathogenetic rationale and an algorithm for acne-like rash correction. Onkogematolog iya = Oncohematology. 2021;16(4):50-8 (in Russian)]. DOI:10.17650/1818-8346-2021-16-4-50-58
19. Ommori R, Nakamura Y, Miyagawa F, et al. Reduced induction of human β-defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies. Clin Exp Dermatol. 2020;45(8):1055-8. DOI:10.1111/ced.14311
20. Jia Z, Bao K, Wei P, et al. EGFR activation-induced decreases in claudin1 promote MUC5AC expression and exacerbate asthma in mice. Mucosal Immunol. 2021;14(1):125-34. DOI:10.1038/s41385-020-0272-z
21. Gerber PA, Kukova G, Buhren BA, Homey B. Density of Demodex folliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology. 2011;222(2):144-7. DOI:10.1159/000323001
22. Ramadan M, Hetta HF, Saleh MM, et al. Alterations in skin microbiome mediated by radiotherapy and their potential roles in the prognosis of radiotherapy-induced dermatitis: a pilot study. Sci Rep. 2021;11(1):5179. DOI:10.1038/s41598-021-84529-7
23. Zhang M, Jiang Z, Li D, et al. Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing. Microb Ecol. 2015;69(2):415-21.
DOI:10.1007/s0024 8-014-0504-4
24. Briaud P, Bastien S, Camus L, et al. Impact of coexistence phenotype between Staphylococcus aureus and Pseudomonas aeruginosa isolates on clinical outcomes among cystic fibrosis patients. Front Cell Infect Microbiol. 2020;10:266. DOI:10.3389/fcimb.2020.00266
25. Armbruster CR, Wolter DJ, Mishra M, et al. Staphylococcus aureus Protein A mediates interspecies interactions at the cell surface of Pseudomonas aeruginosa. mBio. 2016;7(3):e00538-16. DOI:10.1128/mBio.00538-16
________________________________________________
2. Costello EK, Lauber CL, Hamady M, et al. Bacterial community variation in human body habitats across space and time. Science. 2009;326(5960):1694-7. DOI:10.1126/science.1177486
3. Nakatsuji T, Chiang HI, Jiang SB, et al. The microbiome extends to subepidermal compartments of normal skin. Nat Commun. 2013;4:1431. DOI:10.1038/ncomms2441
4. Khlebnikova AN, Petrunin DD. Physiological and pathogenic role of cutaneous microbiota. Treatment algorithms of secondary infected dermatoses. Consilium Medicum. Dermatology (Suppl.). 2016;4:18-25 (in Russian).
5. Murashkin NN, Epishev RV, Ivanov RA, et al. Innovations in Therapeutic Improvement of the Cutaneous Microbiome in Children with Atopic Dermatitis. Current Pediatrics. 2022;21(5):352-61 (in Russian). DOI:10.15690/vsp.v21i5.2449
6. Woo YR, Cho SH, Lee JD, Kim HS. The Human Microbiota and Skin Cancer. Int J Mol Sci. 2022;23(3):1813. DOI:10.3390/ijms23031813
7. Kehrmann J, Koch F, Zumdick S, et al. Reduced Staphylococcus Abundance Characterizes the Lesional Microbiome of Actinic Keratosis Patients after Field-Directed Therapies. Microbiol Spectr. 2023;11(3):e0440122. DOI:10.1128/spectrum.04401-22
8. Kullander J, Forslund O, Dillner J. Staphylococcus aureus and squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev. 2009;18(2):472-8.
DOI:10.1158/1055-9965.EPI-08-0905
9. Wood DLA, Lachner N, Tan JM, et al. A natural history of actinic keratosis and cutaneous squamous cell carcinoma microbiomes. mBio. 2018;9(5):e01432-18. DOI:10.1128/mBio.01432-18
10. Madhusudhan N, Pausan MR, Halwachs B, et al. Molecular profiling of keratinocyte skin tumors links Staphylococcus aureus overabundance and increased human b-defensin-2 expression to growth promotion of squamous cell carcinoma. Cancers (Basel). 2020;12(3):541. DOI:10.3390/cancers12030541
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Авторы
А.С. Полонская*1, А.В. Миченко1,2,3, Л.С. Круглова1, Е.А. Шатохина1,3, А.Н. Львов1,3
1ФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента Российской Федерации, Москва, Россия;
2Международный институт психосоматического здоровья, Москва, Россия;
3Медицинский научно-образовательный центр Московского государственного университета им. М.В. Ломоносова, Москва, Россия
*dr.polonskaia@gmail.com
1Central State Medical Academy, Moscow, Russia;
2International Institute of Psychosomatic Health, Moscow, Russia;
3Medical Research and Educational Center (Lomonosov University Clinic), Moscow, Russia
*dr.polonskaia@gmail.com
1ФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента Российской Федерации, Москва, Россия;
2Международный институт психосоматического здоровья, Москва, Россия;
3Медицинский научно-образовательный центр Московского государственного университета им. М.В. Ломоносова, Москва, Россия
*dr.polonskaia@gmail.com
________________________________________________
1Central State Medical Academy, Moscow, Russia;
2International Institute of Psychosomatic Health, Moscow, Russia;
3Medical Research and Educational Center (Lomonosov University Clinic), Moscow, Russia
*dr.polonskaia@gmail.com
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