> Our Work > The Work We Fund

2024 Larry & Sherry Benaroya – PCF Challenge Award

Characterizing B-Cell Receptor Repertoire to Understand Immunotherapy Response in Prostate Cancer

Principal Investigators: Lucia Nappi, MD, PhD (University of British Columbia, Canada)

Co-Investigators: Faraz Hach, PhD (University of British Columbia, Canada), Amina Zoubeidi, PhD (University of British Columbia, Canada), Julie Graff, MD (Oregon Health & Science University)

Young Investigators: Morgan Roberts, PhD (Vancouver Prostate Centre, Canada)

Collaborators: Martin Gleave, MD (University of British Columbia, Canada), Kim Chi, MD (BC Cancer, Canada), Alexander Wyatt, PhD (University of British Columbia, Canada), Robert Bell, MSc (Vancouver Prostate Centre, Canada)

Description:

  • Prostate cancer is considered an “immune-cold” tumor because of the usually minimal intra-tumor immune cell infiltration and limited efficacy of the immune-checkpoint inhibitors (ICI) observed in unselected patients. 
  • While most studies have focused on T-cells, new insights from known immune responsive tumor types have shown a growing role of B-cells in anti-cancer activity. 
  • B cells are an immune cell type that produce antibodies which are either secreted or remain attached to the cell surface as a “B-cell receptor” (BCR). The BCR gene is different in every B cell born, due to a unique gene rearrangement phenomenon. This mechanism enables the body to produce B cells against theoretically any antigen, but only those stimulated by non-self-antigens in the context of infections or other cellular dangers, will multiply and participate in immune responses.
  • In addition to antibody production, B cells are also very effective in activating T cells and have direct anti-cancer activity. 
  • Dr. Lucia Nappi and team are investigating the role for B cells in mediating responses to immunotherapy in patients with prostate cancer.
  • In this project, the team will investigate the relationship between the BCR gene repertoire and responses to ICI in patients with prostate cancer in several clinical trials.
  • Spatial molecular profiling will be performed on tumor biopsies taken before vs after ICI treatment to characterize tumor, B-cells and other immune cells signatures, and determine any relationships with the BCR repertoire and treatment responses. 
  • Phenotypic changes and activities of peripheral B-cells, T-cells and other immune cells from these patients will be analyzed to determine the interplay between B-cells and T-cells in enhancing anti-cancer activity.
  • If successful, this project will clarify the role of B-cells in dictating response to ICI in prostate cancer patients and will identify BCR characteristics that could be used as predictive biomarkers of response to ICI and to develop new BCR-focused therapies.

What this means to patients: Immune checkpoint immunotherapy (ICI) has the potential to cause long-term tumor regression and even cures in patients with certain types of cancer, but has yet to be optimized in prostate cancer. Dr. Nappi and team are investigating the molecular interplays between B-cells, T-cells and prostate cancer cells in patients with prostate cancer undergoing treatment with ICI, and will determine whether B cell features may serve as biomarkers for selecting patients more likely to benefit from ICI. This could also lead to the discovery of new B cell-focused immunotherapy strategies for prostate cancer.