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 |
