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Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma

Owing to broad and notable clinical anti-tumor activity, anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) antibodies have been indicated for almost all types of cancer, and form a part of the current standard of care. However, a large proportion of patients do not resp...

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Autores principales: Yang, Yonghao, Huang, Hao, Li, Tiepeng, Gao, Quanli, Song, Yongping, Wang, Zibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576543/
https://www.ncbi.nlm.nih.gov/pubmed/34764951
http://dx.doi.org/10.3389/fimmu.2021.728750
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author Yang, Yonghao
Huang, Hao
Li, Tiepeng
Gao, Quanli
Song, Yongping
Wang, Zibing
author_facet Yang, Yonghao
Huang, Hao
Li, Tiepeng
Gao, Quanli
Song, Yongping
Wang, Zibing
author_sort Yang, Yonghao
collection PubMed
description Owing to broad and notable clinical anti-tumor activity, anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) antibodies have been indicated for almost all types of cancer, and form a part of the current standard of care. However, a large proportion of patients do not respond to anti-PD-1/PD-L1 therapy (primary resistance), and responders often develop progressive disease (acquired resistance). The mechanisms of resistance are complex and largely unknown; therefore, overcoming resistance remains clinically challenging, and data on reversing anti-PD-1 resistance are scarce. Herein, we report the case of a 58-year-old woman with renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion, who had already showed resistance to both anti-PD-1 monotherapy and standard-dose axitinib. However, she finally achieved a partial response with a continuous combination therapy comprising low-dose axitinib and anti-PD-1. We speculate that axitinib played a key role in reversing the primary resistance to anti-PD-1 therapy. Interestingly, we observed that the number of peripheral regulatory T cells increased after the standard-dose axitinib therapy, with accompanied tumor enlargement; however, after the dose was reduced, the number of regulatory T cells decreased gradually, and the tumor regressed. We also reviewed relevant literature, which supported the fact that low-dose axitinib might be more beneficial than standard-dose axitinib in assisting immunotherapy. Given that this is a single-case report, the immunomodulatory effect of axitinib requires further investigation.
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spelling pubmed-85765432021-11-10 Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma Yang, Yonghao Huang, Hao Li, Tiepeng Gao, Quanli Song, Yongping Wang, Zibing Front Immunol Immunology Owing to broad and notable clinical anti-tumor activity, anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) antibodies have been indicated for almost all types of cancer, and form a part of the current standard of care. However, a large proportion of patients do not respond to anti-PD-1/PD-L1 therapy (primary resistance), and responders often develop progressive disease (acquired resistance). The mechanisms of resistance are complex and largely unknown; therefore, overcoming resistance remains clinically challenging, and data on reversing anti-PD-1 resistance are scarce. Herein, we report the case of a 58-year-old woman with renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion, who had already showed resistance to both anti-PD-1 monotherapy and standard-dose axitinib. However, she finally achieved a partial response with a continuous combination therapy comprising low-dose axitinib and anti-PD-1. We speculate that axitinib played a key role in reversing the primary resistance to anti-PD-1 therapy. Interestingly, we observed that the number of peripheral regulatory T cells increased after the standard-dose axitinib therapy, with accompanied tumor enlargement; however, after the dose was reduced, the number of regulatory T cells decreased gradually, and the tumor regressed. We also reviewed relevant literature, which supported the fact that low-dose axitinib might be more beneficial than standard-dose axitinib in assisting immunotherapy. Given that this is a single-case report, the immunomodulatory effect of axitinib requires further investigation. Frontiers Media S.A. 2021-10-26 /pmc/articles/PMC8576543/ /pubmed/34764951 http://dx.doi.org/10.3389/fimmu.2021.728750 Text en Copyright © 2021 Yang, Huang, Li, Gao, Song and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yang, Yonghao
Huang, Hao
Li, Tiepeng
Gao, Quanli
Song, Yongping
Wang, Zibing
Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title_full Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title_fullStr Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title_full_unstemmed Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title_short Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
title_sort axitinib reverses resistance to anti-programmed cell death-1 therapy in a patient with renal cell carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576543/
https://www.ncbi.nlm.nih.gov/pubmed/34764951
http://dx.doi.org/10.3389/fimmu.2021.728750
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