A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective...

Autores
Villoldo, Gustavo; Pombo, Maria Teresa; Aris, Mariana; Chemi, Joaquin; Mandó, Pablo; Nagaraju, Supriya; Camean, Juan; Burioni, Adrián; Egea, Débora Mariana; Amat, Mora; Mellado, José León; Mordoh, Jose; Villaronga, Alberto; Barrio, Maria Marcela
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/ PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.
Fil: Villoldo, Gustavo. Instituto Alexander Fleming; Argentina
Fil: Pombo, Maria Teresa. Instituto Alexander Fleming; Argentina
Fil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Fundación Cáncer; Argentina
Fil: Chemi, Joaquin. Instituto Alexander Fleming; Argentina
Fil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Nagaraju, Supriya. University Of Texas. Md Anderson Cancer Center;
Fil: Camean, Juan. Instituto Alexander Fleming; Argentina
Fil: Burioni, Adrián. Instituto Alexander Fleming; Argentina
Fil: Egea, Débora Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Alexander Fleming; Argentina
Fil: Amat, Mora. Instituto Alexander Fleming; Argentina
Fil: Mellado, José León. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Villaronga, Alberto. Instituto Alexander Fleming; Argentina
Fil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Materia
NON-MUSCLE INVASIVE BLADDER CANCER
BCG PREDICTIVE BIOMARKERS
LYMPHOCYTE POLARIZATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/237184
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/237184
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective studyVilloldo, GustavoPombo, Maria TeresaAris, MarianaChemi, JoaquinMandó, PabloNagaraju, SupriyaCamean, JuanBurioni, AdriánEgea, Débora MarianaAmat, MoraMellado, José LeónMordoh, JoseVillaronga, AlbertoBarrio, Maria MarcelaNON-MUSCLE INVASIVE BLADDER CANCERBCG PREDICTIVE BIOMARKERSLYMPHOCYTE POLARIZATIONhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/ PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.Fil: Villoldo, Gustavo. Instituto Alexander Fleming; ArgentinaFil: Pombo, Maria Teresa. Instituto Alexander Fleming; ArgentinaFil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Fundación Cáncer; ArgentinaFil: Chemi, Joaquin. Instituto Alexander Fleming; ArgentinaFil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Nagaraju, Supriya. University Of Texas. Md Anderson Cancer Center;Fil: Camean, Juan. Instituto Alexander Fleming; ArgentinaFil: Burioni, Adrián. Instituto Alexander Fleming; ArgentinaFil: Egea, Débora Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Alexander Fleming; ArgentinaFil: Amat, Mora. Instituto Alexander Fleming; ArgentinaFil: Mellado, José León. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Villaronga, Alberto. Instituto Alexander Fleming; ArgentinaFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaTech Science Press2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/237184Villoldo, Gustavo; Pombo, Maria Teresa; Aris, Mariana; Chemi, Joaquin; Mandó, Pablo; et al.; A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study; Tech Science Press; Oncology Research; 31; 2; 3-2023; 207-2200965-04071555-3906CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.32604/or.2023.028163info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/or/v31n2/52290info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:03:58Zoai:ri.conicet.gov.ar:11336/237184instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:03:58.886CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
title A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
spellingShingle A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
Villoldo, Gustavo
NON-MUSCLE INVASIVE BLADDER CANCER
BCG PREDICTIVE BIOMARKERS
LYMPHOCYTE POLARIZATION
title_short A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
title_full A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
title_fullStr A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
title_full_unstemmed A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
title_sort A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study
dc.creator.none.fl_str_mv Villoldo, Gustavo
Pombo, Maria Teresa
Aris, Mariana
Chemi, Joaquin
Mandó, Pablo
Nagaraju, Supriya
Camean, Juan
Burioni, Adrián
Egea, Débora Mariana
Amat, Mora
Mellado, José León
Mordoh, Jose
Villaronga, Alberto
Barrio, Maria Marcela
author Villoldo, Gustavo
author_facet Villoldo, Gustavo
Pombo, Maria Teresa
Aris, Mariana
Chemi, Joaquin
Mandó, Pablo
Nagaraju, Supriya
Camean, Juan
Burioni, Adrián
Egea, Débora Mariana
Amat, Mora
Mellado, José León
Mordoh, Jose
Villaronga, Alberto
Barrio, Maria Marcela
author_role author
author2 Pombo, Maria Teresa
Aris, Mariana
Chemi, Joaquin
Mandó, Pablo
Nagaraju, Supriya
Camean, Juan
Burioni, Adrián
Egea, Débora Mariana
Amat, Mora
Mellado, José León
Mordoh, Jose
Villaronga, Alberto
Barrio, Maria Marcela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NON-MUSCLE INVASIVE BLADDER CANCER
BCG PREDICTIVE BIOMARKERS
LYMPHOCYTE POLARIZATION
topic NON-MUSCLE INVASIVE BLADDER CANCER
BCG PREDICTIVE BIOMARKERS
LYMPHOCYTE POLARIZATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/ PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.
Fil: Villoldo, Gustavo. Instituto Alexander Fleming; Argentina
Fil: Pombo, Maria Teresa. Instituto Alexander Fleming; Argentina
Fil: Aris, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Fundación Cáncer; Argentina
Fil: Chemi, Joaquin. Instituto Alexander Fleming; Argentina
Fil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Nagaraju, Supriya. University Of Texas. Md Anderson Cancer Center;
Fil: Camean, Juan. Instituto Alexander Fleming; Argentina
Fil: Burioni, Adrián. Instituto Alexander Fleming; Argentina
Fil: Egea, Débora Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Alexander Fleming; Argentina
Fil: Amat, Mora. Instituto Alexander Fleming; Argentina
Fil: Mellado, José León. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Villaronga, Alberto. Instituto Alexander Fleming; Argentina
Fil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
description Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/ PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/237184
Villoldo, Gustavo; Pombo, Maria Teresa; Aris, Mariana; Chemi, Joaquin; Mandó, Pablo; et al.; A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study; Tech Science Press; Oncology Research; 31; 2; 3-2023; 207-220
0965-0407
1555-3906
CONICET Digital
CONICET
url http://hdl.handle.net/11336/237184
identifier_str_mv Villoldo, Gustavo; Pombo, Maria Teresa; Aris, Mariana; Chemi, Joaquin; Mandó, Pablo; et al.; A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study; Tech Science Press; Oncology Research; 31; 2; 3-2023; 207-220
0965-0407
1555-3906
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.32604/or.2023.028163
info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/or/v31n2/52290
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Tech Science Press
publisher.none.fl_str_mv Tech Science Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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