| Popis: |
Intravesical BCG is the gold standard therapy for intermediate/high-risk 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 a predictive biomarker of BCG response by analyzing TILs polarization in the TME in pre-treatment biopsies. Materials and Methods: Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillations 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 the BCG response. In most nonresponders, 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 higher 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 with 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 BCG response.Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity. |
