Submission ID 93087

Poster Code HR-P-100
Title of Abstract Investigating the role of atypical B cells in response to BCG in non muscle invasive bladder cancer
Abstract Submission Background: Non-muscle invasive bladder cancer (NMIBC) comprises 75% of bladder cancer (BC) cases being diagnosed worldwide. Intravesical bacilllus Calmette-Guerin (BCG) immunotherapy is the gold standard treatment for intermediate and high-risk NMIBC. Despite its proven efficacy, over 50% patients receiving BCG immunotherapy experience early recurrence or progression. In our recent study, we highlighted high intra-tumoral B cell density to be associated with early recurrence and progression of NMIBC. Since, atypical B cells (ABCs), a subset of B cells are known to expand with biological aging, repetitive immunization and/or in autoimmune diseases, we hypothesized that ABCs are recruited to the bladder mucosa during repeated BCG instillation in the induction phase of treatment and dampen the local anti-tumor immunity leading to poor response to BCG. Methods: The N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen induced murine model of BC was used to investigate the role of B cells in mediating BCG response. Female and male mice exposed to BBN were treated with intravesical BCG immunotherapy with or without B cell depletion. Systemic and local immune profiling was done using multispectral flow cytometry and multiplex immunofluorescence. Plasma cytokine levels were analyzed using multiplex cytokine profiling. Results: Increased infiltration of B cells and expansion of ABCs systemically and locally (bladder) was observed after repeated BCG instillations. In vivo depletion of B cells during BCG treatment in mice exposed to BBN showed enhanced recovery of the urothelium with high CD11b+ myeloid cell infiltration. Depletion of B cells during BCG treatment also altered the frequency of T cell subsets and depicted elevated levels of plasma Th1 and Th2 cytokines. Conclusion: Results from in vivo studies demonstrated a potential role of ABCs in mediating poor response to BCG. Therapeutic targeting of ABC associated markers could be a novel approach for treatment of NMIBC patients.
Please indicate who nominated you Department of Biomedical and Molecular Science, Queen's University
What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? Cancer Research
Gender and Health
What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? Biomedical
PDF of abstract PYolmo_iCAM2023.pdf
2023-02-02 at 20:27:54
Presenter and Author(s) Priyanka Yolmo
Priyanka Yolmo
Sadaf Rahimi
Gwenaelle Conseil
Kartik Sachdeva
Dr. Robert Siemens
Dr. Madhuri Koti

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