The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy

Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinica...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Wang, Xueping [verfasserIn] Wang, Fang [verfasserIn] Zhong, Mengjun [verfasserIn] Yarden, Yosef [verfasserIn] Fu, Liwu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Immunotherapy PD-1/PD-L1 Hyperprogressive disease Biomarker

Übergeordnetes Werk:	Enthalten in: Molecular cancer - London : Biomed Central, 2002, 19(2020), 1 vom: 02. Mai
Übergeordnetes Werk:	volume:19 ; year:2020 ; number:1 ; day:02 ; month:05

Links:	Volltext

DOI / URN:	10.1186/s12943-020-01200-x

Katalog-ID:	SPR03959775X

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allfields	10.1186/s12943-020-01200-x doi (DE-627)SPR03959775X (SPR)s12943-020-01200-x-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.00 bkl Wang, Xueping verfasserin aut The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments. Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Wang, Fang verfasserin aut Zhong, Mengjun verfasserin aut Yarden, Yosef verfasserin aut Fu, Liwu verfasserin aut Enthalten in Molecular cancer London : Biomed Central, 2002 19(2020), 1 vom: 02. Mai (DE-627)355987619 (DE-600)2091373-4 1476-4598 nnns volume:19 year:2020 number:1 day:02 month:05 https://dx.doi.org/10.1186/s12943-020-01200-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 19 2020 1 02 05
spelling	10.1186/s12943-020-01200-x doi (DE-627)SPR03959775X (SPR)s12943-020-01200-x-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.00 bkl Wang, Xueping verfasserin aut The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments. Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Wang, Fang verfasserin aut Zhong, Mengjun verfasserin aut Yarden, Yosef verfasserin aut Fu, Liwu verfasserin aut Enthalten in Molecular cancer London : Biomed Central, 2002 19(2020), 1 vom: 02. Mai (DE-627)355987619 (DE-600)2091373-4 1476-4598 nnns volume:19 year:2020 number:1 day:02 month:05 https://dx.doi.org/10.1186/s12943-020-01200-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 19 2020 1 02 05
allfields_unstemmed	10.1186/s12943-020-01200-x doi (DE-627)SPR03959775X (SPR)s12943-020-01200-x-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.00 bkl Wang, Xueping verfasserin aut The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments. Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Wang, Fang verfasserin aut Zhong, Mengjun verfasserin aut Yarden, Yosef verfasserin aut Fu, Liwu verfasserin aut Enthalten in Molecular cancer London : Biomed Central, 2002 19(2020), 1 vom: 02. Mai (DE-627)355987619 (DE-600)2091373-4 1476-4598 nnns volume:19 year:2020 number:1 day:02 month:05 https://dx.doi.org/10.1186/s12943-020-01200-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 19 2020 1 02 05
allfieldsGer	10.1186/s12943-020-01200-x doi (DE-627)SPR03959775X (SPR)s12943-020-01200-x-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.00 bkl Wang, Xueping verfasserin aut The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments. Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Wang, Fang verfasserin aut Zhong, Mengjun verfasserin aut Yarden, Yosef verfasserin aut Fu, Liwu verfasserin aut Enthalten in Molecular cancer London : Biomed Central, 2002 19(2020), 1 vom: 02. Mai (DE-627)355987619 (DE-600)2091373-4 1476-4598 nnns volume:19 year:2020 number:1 day:02 month:05 https://dx.doi.org/10.1186/s12943-020-01200-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 19 2020 1 02 05
allfieldsSound	10.1186/s12943-020-01200-x doi (DE-627)SPR03959775X (SPR)s12943-020-01200-x-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.00 bkl Wang, Xueping verfasserin aut The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments. Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Wang, Fang verfasserin aut Zhong, Mengjun verfasserin aut Yarden, Yosef verfasserin aut Fu, Liwu verfasserin aut Enthalten in Molecular cancer London : Biomed Central, 2002 19(2020), 1 vom: 02. Mai (DE-627)355987619 (DE-600)2091373-4 1476-4598 nnns volume:19 year:2020 number:1 day:02 month:05 https://dx.doi.org/10.1186/s12943-020-01200-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 19 2020 1 02 05
language	English
source	Enthalten in Molecular cancer 19(2020), 1 vom: 02. Mai volume:19 year:2020 number:1 day:02 month:05
sourceStr	Enthalten in Molecular cancer 19(2020), 1 vom: 02. Mai volume:19 year:2020 number:1 day:02 month:05
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author	Wang, Xueping
spellingShingle	Wang, Xueping ddc 610 bkl 44.00 misc Immunotherapy misc PD-1/PD-L1 misc Hyperprogressive disease misc Biomarker The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
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topic_title	610 570 ASE 44.00 bkl The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy Immunotherapy (dpeaa)DE-He213 PD-1/PD-L1 (dpeaa)DE-He213 Hyperprogressive disease (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213
topic	ddc 610 bkl 44.00 misc Immunotherapy misc PD-1/PD-L1 misc Hyperprogressive disease misc Biomarker
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title	The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
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title_full	The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
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title_sort	biomarkers of hyperprogressive disease in pd-1/pd-l1 blockage therapy
title_auth	The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
abstract	Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments.
abstractGer	Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments.
abstract_unstemmed	Abstract Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments.
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title_short	The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
url	https://dx.doi.org/10.1186/s12943-020-01200-x
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up_date	2024-07-04T00:41:03.093Z
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The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy

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