Sea Hare Hydrolysate Reduces PD-L1 Levels in Cancer Cells and Mitigates Rheumatoid Arthritis Ina Collagen-Induced
Ji Hyeon Ryu1, Min Seok Song2,3, Marie Merci Nyiramana2,4
1Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital Yangsan Republic of Korea.
Abstract:
Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune-oncology (I-O) agents or adjuvants, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I-O agent or adjuvant. In this study, we investigated the effects of SHH on PD-L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I-O agents. Our results showed a marked reduction in PD-L1 levels in multiple cancer cell lines and decreased PD-1 and PD-L1 levels in tumor-associated macrophages. In a mouse model with collagen-induced arthritis (CIA), SHH exhibited anti-inflammatory effects comparable to methotrexate (MTX), a first-line treatment for RA. Both the SHH and MTX groups had significantly lower arthritis scores and paw thickness compared to the CIA group. Additionally, SHH or MTX treatment effectively reduced elevated levels of anticollagen type II (CII) antibodies and proinflammatory cytokines (IL-1β, IL-6, and TNF-α). Histopathological analysis revealed that SHH and MTX treatments notably mitigated arthritic inflammation, synovial hyperplasia, and loss of articular cartilage and bone. Micro-CT scans showed reduced articular destruction in the SHH and MTX groups. These findings indicate that SHH treatment decreases PD-L1 levels in cancer cells and reduces the severity of CIA by exerting anti-inflammatory effects. Therefore, SHH holds promise as an I-O agent without side effects such as exacerbation of RA.
Insights
Sea hare hydrolysate (SHH) reduces cancer cell PD-L1 levels and treats rheumatoid arthritis (RA) by decreasing inflammation. SHH shows promise as an immune-oncology (I-O) agent without RA exacerbation risks.
Area of Science:
- Immunology
- Oncology
- Rheumatology
Background:
- Previous research indicated sea hare hydrolysate (SHH) has anticancer properties by inhibiting signal transducer and activator of transcription 3 (STAT3), affecting macrophage polarization and pyroptosis in lung cancer.
- Immune-oncology (I-O) agents, like those targeting programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), can increase rheumatoid arthritis (RA) risk.
- Investigating SHH's effects on PD-L1 and its potential as an I-O agent or adjuvant, considering RA as a potential side effect, is crucial.
Purpose of the Study:
- To evaluate the impact of SHH on PD-L1 expression across diverse cancer cell types.
- To assess SHH's therapeutic efficacy in a collagen-induced arthritis (CIA) mouse model, mimicking RA.
- To determine if SHH can serve as an immune-oncology (I-O) agent or adjuvant with a favorable safety profile regarding RA.
Main Methods:
- SHH was applied to various cancer cell lines to measure PD-L1 levels.
- A collagen-induced arthritis (CIA) mouse model was used to evaluate SHH's anti-inflammatory effects compared to methotrexate (MTX).
- Arthritis scores, paw thickness, anti-collagen type II (CII) antibodies, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and histopathological changes were assessed.
Main Results:
- SHH significantly reduced PD-L1 levels in multiple cancer cell lines and decreased PD-1/PD-L1 in tumor-associated macrophages.
- In the CIA mouse model, SHH demonstrated anti-inflammatory effects comparable to MTX, significantly lowering arthritis scores and paw thickness.
- SHH treatment reduced elevated anti-CII antibodies and pro-inflammatory cytokines, mitigating arthritic inflammation, synovial hyperplasia, and cartilage/bone loss.
Conclusions:
- SHH effectively decreases PD-L1 levels in cancer cells and exhibits significant anti-inflammatory properties in a preclinical RA model.
- SHH's therapeutic effects in CIA are comparable to methotrexate, suggesting its potential as a treatment for inflammatory conditions.
- SHH shows promise as an immune-oncology agent or adjuvant, potentially offering therapeutic benefits without the risk of exacerbating RA.
