Similar immune responses to alpha1-oleate and Bacillus Calmette–Guérin treatment in patients with bladder cancer
(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)
- author
- Ahmadi, Shahram LU ; Ambite, Ines LU ; Brisuda, Antonín ; Háček, Jaromír ; Haq, Farhan LU ; Sabari, Samudra LU ; Vanarsa, Kamala ; Mohan, Chandra ; Babjuk, Marek and Svanborg, Catharina LU
- organization
- publishing date
- 2024-04
- 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
-
- scopus:85189495519
- pmid:38553868
- 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}}, }