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- Rådestad, E., et al.
(författare)
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Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue
- 2017
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 8:36, s. 60257-60269
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Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostateinfiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD- 1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.
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- Anheden, Marie, et al.
(författare)
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Value chain for production of bio-oil from kraft lignin for use as bio-jet fuel
- 2017
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Ingår i: The 7th Nordic Wood Biorefinery Conference held in Stockholm, Sweden, 28-30 Mar. 2017. - Stockholm : RISE Bioekonomi. - 9789186018207 ; , s. 104-109
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Konferensbidrag (refereegranskat)abstract
- The LignoJet project aimed to achieve an intermediate lignin-oil product miscible with fossil feedstock and with a significantly reduced oxygen content. A technical concept for production has been studied that involves combined catalysed depolymerisation and hydrodeoxygenation, so called hydrogenolytic depolymerisation, of kraft lignin. Kraft lignin was separated through membrane ultrafiltration from softwood and eucalyptus black liquor followed by precipitation through LignoBoost technology. A difference in lignin properties was observed between ultrafiltration of softwood and eucalyptus black liquor through 15 and 150kDa ceramic membranes. Lignin-oils with similar oxygen content were produced regardless of origin and fractionation technique. A lignin-oil with favourable properties as precursor for refinery integration for jet fuel production as produced in small-scale batch experiments using nickel-based catalyst. Stable pumpable oils with melting point of less than 25-50 deg C and with 20-30% lower oxygen content and aromatic content were obtained that would be suitable as jet fuel precursors. The estimated production cost was found to be competitive with that of other liquid biofuels, while additional revenues could potentially be achieved by also producing chemical and materials from suitable fractions of the lignin-oil.
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- Arruda, L. C. M., et al.
(författare)
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Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution
- 2019
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Ingår i: Journal of Immunology. - : NLM (Medline). - 0022-1767 .- 1550-6606. ; 202:6, s. 1859-1870
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Tidskriftsartikel (refereegranskat)abstract
- Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/- The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. This was more prominent in grafts from CMV+ donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission.
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