Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Similar immune responses to alpha1-oleate and Bacillus Calmette–Guérin treatment in patients with bladder cancer

Ahmadi, Shahram LU ; Ambite, Ines LU orcid ; Brisuda, Antonín ; Háček, Jaromír ; Haq, Farhan LU ; Sabari, Samudra LU ; Vanarsa, Kamala ; Mohan, Chandra ; Babjuk, Marek and Svanborg, Catharina LU (2024) In Cancer Medicine 13(7).
Abstract

Background: The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. Methods: In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. Results: Proteomic profiling detected a... (More)

Background: The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. Methods: In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. Results: Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL-1RA and pro-inflammatory cytokines in the IL-1 family (IL-1α, IL-1β, IL-33), chemokines (MIP-1α, IL-8), and interferons (IFN-α2, IFN-γ). Adaptive immune mediators included IL-12, Granzyme B, CD40, PD-L1, and IL-17D, suggesting broad effects of alpha 1-oleate treatment on the tumor tissues. Conclusions: The cytokine response profile in alpha 1-oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer-related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1-oleate is shown to activate a broad immune response with a protective potential.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha1-oleate, BCG, bladder cancer, immune response, proteomic analysis
in
Cancer Medicine
volume
13
issue
7
article number
e7091
publisher
Wiley-Blackwell
external identifiers
  • pmid:38553868
  • scopus:85189495519
ISSN
2045-7634
DOI
10.1002/cam4.7091
language
English
LU publication?
yes
id
c2d6ae61-ce34-4783-a624-d5f28c3005cd
date added to LUP
2024-04-25 15:37:53
date last changed
2024-07-04 21:25:30
@article{c2d6ae61-ce34-4783-a624-d5f28c3005cd,
  abstract     = {{<p>Background: The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. Methods: In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. Results: Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL-1RA and pro-inflammatory cytokines in the IL-1 family (IL-1α, IL-1β, IL-33), chemokines (MIP-1α, IL-8), and interferons (IFN-α2, IFN-γ). Adaptive immune mediators included IL-12, Granzyme B, CD40, PD-L1, and IL-17D, suggesting broad effects of alpha 1-oleate treatment on the tumor tissues. Conclusions: The cytokine response profile in alpha 1-oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer-related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1-oleate is shown to activate a broad immune response with a protective potential.</p>}},
  author       = {{Ahmadi, Shahram and Ambite, Ines and Brisuda, Antonín and Háček, Jaromír and Haq, Farhan and Sabari, Samudra and Vanarsa, Kamala and Mohan, Chandra and Babjuk, Marek and Svanborg, Catharina}},
  issn         = {{2045-7634}},
  keywords     = {{alpha1-oleate; BCG; bladder cancer; immune response; proteomic analysis}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cancer Medicine}},
  title        = {{Similar immune responses to alpha1-oleate and Bacillus Calmette–Guérin treatment in patients with bladder cancer}},
  url          = {{http://dx.doi.org/10.1002/cam4.7091}},
  doi          = {{10.1002/cam4.7091}},
  volume       = {{13}},
  year         = {{2024}},
}