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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/237184
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oai:ri.conicet.gov.ar:11336/237184 |
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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 Técnicas2025-09-29T09:35:54Zoai: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:34982025-09-29 09:35:54.947CONICET 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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1844613122707423232 |
score |
13.070432 |