| 1. |
- Femel, Julia, 1986-, et al.
(författare)
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Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden
- 2022
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 71:8, s. 2029-2040
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic strategies directed against Gal1 would enable simultaneous targeting of angiogenesis, immune evasion and metastasis. In the current study, we have analyzed the potential of Gal1 as a cancer vaccine target. We show that it is possible to generate high anti-Gal1 antibody levels in mice immunized with a recombinant vaccine protein consisting of bacterial sequences fused to Gal1. Growth of Gal1 expressing melanomas was significantly impaired in the immunized mice compared to the control group. This was associated with improved perfusion of the tumor vasculature, as well as increased infiltration of macrophages and cytotoxic T cells (CTLs). The level of granzyme B, mainly originating from CTLs in our model, was significantly elevated in Gal1 vaccinated mice and correlated with a decrease in tumor burden. We conclude that vaccination against Gal1 is a promising pro-immunogenic approach for cancer therapy that could potentially enhance the effect of other immunotherapeutic strategies due to its ability to promote CTL influx in tumors.
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| 2. |
- Dandebo, Lovisa, et al.
(författare)
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The impact of a road safety policy implementation within an international organization
- 2021
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Ingår i: Journal of Public Health-Heidelberg. - : Springer Science and Business Media LLC. - 2198-1833 .- 1613-2238. ; 29, s. 951-956
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Tidskriftsartikel (refereegranskat)abstract
- Aim This study was performed within an international organization (IO), headquartered in Washington, D.C. The employees are facing great risks during their missions abroad, where developing countries are the most common travel destination. The IO conducted a staff road safety survey in 2008 and based a road safety policy on the results of this survey. In 2017, a follow-up survey investigated the impact of the policy implementation. The aim of this study was to investigate the effect of that policy. Subjects and methods This study is based on two cross-sectional road safety surveys conducted by the IO's Staff Road Safety Task Force. The study population consisted of both regular employees and consultants based at country offices (CO) worldwide. The number of reported road traffic crashes and near-crashes (nearly had a crash), as well as road safety behavior, was compared between these two surveys. The analysis was performed from a gender perspective. High-risk countries were identified based on the number of reported road traffic crashes and near-crashes. Results Over a period of nine years, the incidence rates had dropped from 1.6 to 0.7 road traffic crashes per 1000 travel days and from 14 to 8.9 near-crashes per 1000 travel days. Seat belt usage had increased from 70% to 80%. There were no major differences between male and female respondents. Developing countries had the highest travel adjusted event rates. Conclusion The findings of this study suggest that the policy had a positive impact on road safety among CO staff within the IO.
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| 3. |
- Raykova, Doroteya, 1986-, et al.
(författare)
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A method for Boolean analysis of protein interactions at a molecular level
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Determination of interactions between native proteins in cells is important for understanding function. Here the authors report MolBoolean as a method to detect interactions between endogenous proteins in subcellular compartments, using antibody-DNA conjugates for identification and signal amplification. Determining the levels of protein-protein interactions is essential for the analysis of signaling within the cell, characterization of mutation effects, protein function and activation in health and disease, among others. Herein, we describe MolBoolean - a method to detect interactions between endogenous proteins in various subcellular compartments, utilizing antibody-DNA conjugates for identification and signal amplification. In contrast to proximity ligation assays, MolBoolean simultaneously indicates the relative abundances of protein A and B not interacting with each other, as well as the pool of A and B proteins that are proximal enough to be considered an AB complex. MolBoolean is applicable both in fixed cells and tissue sections. The specific and quantifiable data that the method generates provide opportunities for both diagnostic use and medical research.
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| 4. |
- Sun, Yi, et al.
(författare)
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Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:604
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Tidskriftsartikel (refereegranskat)abstract
- The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention.
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