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.
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.
Background Inflammatory myofibroblastic tumor (IMT) of the bladder (BIMT) is a rare entity with non-specific symptoms and particular histological features. Though bladder location is very uncommon, it arises from the bladder submucosal stroma as a polypoidal growth and is easily mistaken clinically, radiologically and histologically with a malignant neoplasm. The main treatment is surgical resection. To our knowledge, few reports of this pathology have been duly informed in Latin America to date. Case presentation We present four case male patients evidencing bladder tumor initially treated with transurethral bladder resection, diagnosing BIMT. They had shown tumor recurrence and laparoscopic treatment were decided without evidence of new recurrence. Conclusion Due to the few reports of this pathology, specially in South America, it is important to know its therapeutic management and follow-up.
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