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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

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Oncology Research 2023年第2期31卷 207-220页

作者： GUSTAVO MARTÍN VILLOLDO MARÍA TERESA POMBO MARIANA ARIS JOAQUÍN CHEMI PABLO MANDÓ SUPRIYA NAGARAJU juan camean ADRIÁN BURIONI DEBORAH EGEA MORA AMAT JOSÉLEÓN MELLADO JOSÉMORDOH ALBERTO VILLARONGA MARÍA MARCELA BARRIO Urology Department Instituto Alexander FlemingCiudad Autónoma de Buenos Aires1426Argentina Immunohistochemistry Department Instituto Alexander FlemingCiudad Autónoma de Buenos Aires1426Argentina Centro de Investigaciones Oncológicas Fundación Cáncer FUCACiudad Autónoma de Buenos Aires1426Argentina Urology Department MD Anderson Cancer CenterHoustonTX77030USA Pathology Department Instituto Alexander FlemingCiudad Autónoma de Buenos Aires1426Argentina

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 *** induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor *** searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment ***-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by *** polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+*** addition,PD-1/PD-L1 staining was *** results correlated with BCG *** most non-responders,Th1/Th2 markers were compared in pre-and post-BCG *** was 65.6%in the study *** responders had a higher G/T ratio and a greater number of degranulated EPX+*** 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 ***-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 ***-L1/PD-1 expression was not associated with the response to *** 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.

关键词： Non-muscle invasive bladder cancer BCG predictive biomarkers Lymphocyte polarization

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