Carcinogen induced expansion of atypical B cells and pre-treatment tumor adjacent tertiary lymphoid structures associate with poor response to BCG in non-muscle invasive bladder cancer (original) (raw)

Intravesical bacillus Calmette-Guérin (BCG) G immunotherapy is the gold standard treatment for patients with non-muscle invasive bladder cancer (NMIBC). Unfortunately, more than 50% patients experience early recurrence or progression. Increased intra-tumoral immune infiltration in pre-treatment tumors has been shown to associate with poor outcomes post BCG therapy. Specifically, we recently showed that high intra-tumoral B cell density was associated with early recurrence and progression of NMIBC. Here, we address a major knowledge gap in the role of BCG induced expansion of a B cell population called, ‘atypical B cells (ABCs)’ in the context of age and sex, the two major variables in the pathophysiology of NMIBC. We first investigated whether pre-BCG TLSs associate with response to BCG. Using multiplex immunofluorescence and NanoString GeoMx digital spatial profiling-based characterization, we found higher density of tumor adjacent (TA) TLSs in patients categorized as BCG non-respo...