(UroToday.com) The 2024 IBCN annual meeting included a session on advancements in circulating biomarkers, featuring a presentation by Dr. Priyanka Yolmo discussing BCG-induced B cell responses in patients with non-muscle invasive bladder cancer. Despite the proven efficacy of BCG immunotherapy treatment for non-muscle invasive bladder cancer (NMIBC), over 50% of patients experience early disease recurrence or progression. An improved understanding of BCG-induced anti-tumor mucosal immune responses is needed to identify biomarkers of response and alternative therapies.
This group’s previous research revealed high intra-tumoral B cell density correlates with shorter recurrence- and progression-free survival in BCG-treated patients. Using a carcinogen-induced murine model, they reported that repeated BCG administration expanded an exhausted B cell subset, atypical B cells in the bladder microenvironment. Depletion of exhausted B cells during BCG treatment in BBN-exposed mice promoted urothelial recovery and reduced PD-L1 immune checkpoint expression. In humans, atypical B-Cells may be secondary to (i) chronic inflammation, (ii) biological aging, and (iii) repeated immunization:
The hypothesis of the current study is that expansion of atypical B cells during repeated BCG instillation dampens the anti-tumor immune responses, leading to early recurrence or progression to muscle-invasive disease.
B cells from peripheral blood of patients undergoing BCG treatment were characterized using multispectral flow cytometry. Matched plasma samples were analyzed using the Olink Target-96 Immuno-Oncology panel, and corresponding index TURBT specimens underwent histopathological evaluation.
There were 27 patients included in the current analysis with the following patient flow chart:
Flow cytometry-based profiling of circulating B cells revealed a variable trend in atypical B cell profiles post-BCG treatment, with a significant expansion in the majority of the recurrent cases. Olink platform-based analysis of plasma revealed differential protein expression post-BCG compared to the pre-BCG group. Patients exhibiting early recurrence had significantly increased levels of secreted PD-L1 and IL-6, whereas those who did not recur had elevated CD40, CD5, and IL-12, after four intravesical BCG instillations.
Dr. Yolmo concluded her presentation discussing BCG-induced B cell responses in patients with non-muscle invasive bladder cancer with the following take-home points:
- Atypical B cells drive the tumor immune microenvironment to a suppressive state
- It is important to identify novel targets with the B cell axis to improve response to BCG immunotherapy
Presented by: Priyanka Yolmo, PhD Candidate, Queens University, Kingston, Ontario, Canada
Co-Authors: Kartik Sachdeva¹ ², Sindhuja Pattabhi³, Alanna Brewer⁴, Abdulhameed Abdulhamed⁵, Ashley Griffin⁶, Gwenaëlle Conseil¹ ², Haocheng Yu⁷, David M. Berman⁵, Amir Horowitz⁷, Morgan Roberts³, Peter Black³, D. Robert Siemens² ⁴ ⁶, Me² Madhuri Koti¹ ² ⁶ ⁸
¹ Queen’s Cancer Research Institute, Kingston, ON, Canada
² Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada
³ Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
⁴ Department of Urology, Kingston Health Sciences Center, Kingston, ON, Canada
⁵ Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada
⁶ Department of Urology, Queen’s University, Kingston, ON, Canada
⁷ The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
⁸ Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, WellStar MCG Health, @zklaassen_md on Twitter during the 2024 International Bladder Cancer Network (IBCN) Annual Meeting, Bern, Switzerland, Thurs, Sept 19 – Sat, Sept 21, 2024