Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients an...

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Autores principales:	Laura Theobald, Russalina Stroeder, Patrick Melchior, Ioan Iulian Iordache, Tanja Tänzer, Meike Port, Birgit Glombitza, Stefanie Marx, David Schub, Christian Herr, Martin Hart, Nicole Ludwig, Eckart Meese, Yoo‐Jin Kim, Rainer Maria Bohle, Sigrun Smola, Christian Rübe, Erich Franz Solomayer, Barbara Walch‐Rückheim
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AKT cervical cancer recurrence chemoradiotherapy resistance T‐helper‐17 cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9d39a3e2e8984294abe5e69d7e568744
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spelling	oai:doaj.org-article:9d39a3e2e8984294abe5e69d7e5687442021-12-02T10:31:06ZChemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse1878-02611574-789110.1002/1878-0261.13095https://doaj.org/article/9d39a3e2e8984294abe5e69d7e5687442021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13095https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4+ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer.Laura TheobaldRussalina StroederPatrick MelchiorIoan Iulian IordacheTanja TänzerMeike PortBirgit GlombitzaStefanie MarxDavid SchubChristian HerrMartin HartNicole LudwigEckart MeeseYoo‐Jin KimRainer Maria BohleSigrun SmolaChristian RübeErich Franz SolomayerBarbara Walch‐RückheimWileyarticleAKTcervical cancer recurrencechemoradiotherapyresistanceT‐helper‐17 cellsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3559-3577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AKT cervical cancer recurrence chemoradiotherapy resistance T‐helper‐17 cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	AKT cervical cancer recurrence chemoradiotherapy resistance T‐helper‐17 cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Laura Theobald Russalina Stroeder Patrick Melchior Ioan Iulian Iordache Tanja Tänzer Meike Port Birgit Glombitza Stefanie Marx David Schub Christian Herr Martin Hart Nicole Ludwig Eckart Meese Yoo‐Jin Kim Rainer Maria Bohle Sigrun Smola Christian Rübe Erich Franz Solomayer Barbara Walch‐Rückheim Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
description	Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4+ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer.
format	article
author	Laura Theobald Russalina Stroeder Patrick Melchior Ioan Iulian Iordache Tanja Tänzer Meike Port Birgit Glombitza Stefanie Marx David Schub Christian Herr Martin Hart Nicole Ludwig Eckart Meese Yoo‐Jin Kim Rainer Maria Bohle Sigrun Smola Christian Rübe Erich Franz Solomayer Barbara Walch‐Rückheim
author_facet	Laura Theobald Russalina Stroeder Patrick Melchior Ioan Iulian Iordache Tanja Tänzer Meike Port Birgit Glombitza Stefanie Marx David Schub Christian Herr Martin Hart Nicole Ludwig Eckart Meese Yoo‐Jin Kim Rainer Maria Bohle Sigrun Smola Christian Rübe Erich Franz Solomayer Barbara Walch‐Rückheim
author_sort	Laura Theobald
title	Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
title_short	Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
title_full	Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
title_fullStr	Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
title_full_unstemmed	Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
title_sort	chemoradiotherapy‐induced increase in th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/9d39a3e2e8984294abe5e69d7e568744
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Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse

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