@Article{or.2023.028163,
AUTHOR = {GUSTAVO MARTÍN VILLOLDO, MARÍA TERESA POMBO, MARIANA ARIS, JOAQUÍN CHEMI, PABLO MANDÓ, SUPRIYA NAGARAJU, JUAN CAMEAN, ADRIÁN BURIONI, DEBORAH EGEA, MORA AMAT, JOSÉ LEÓN MELLADO, JOSÉ MORDOH, ALBERTO VILLARONGA, MARÍA MARCELA BARRIO},
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},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {2},
PAGES = {207--220},
URL = {http://www.techscience.com/or/v31n2/52290},
ISSN = {1555-3906},
ABSTRACT = {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 (<i>p</i> = 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 (<i>p</i> = 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.},
DOI = {10.32604/or.2023.028163}
}