| 1. |
- Backman, Max, et al.
(författare)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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| 2. |
- Backman, Max, 1987-, et al.
(författare)
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Spatial immunophenotyping of the tumor microenvironment in non-small cell lung cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Immune cells in the tumor microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterize the spatial immune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence multispectral imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4 Eff), CD4 regulatory cells (CD4 Treg), CD8 effector cells (CD8 Eff), CD8 regulatory cells (CD8 Treg), B-cells, NK-cells, NKT-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs). Results: CD4 Eff cells, CD8 Eff cells, and M1 macrophages were the most abundant immune cells invading the tumor cell compartment and indicated a patient group with a favorable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4 Eff, CD4 Treg, CD8 Treg, and B-cells), as well as pDCs, were independently associated with longer survival. However, when these immune cells were located close to CD8 Treg cells, the favorable impact was attenuated. In the multivariate Cox regression model including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8 Treg–B-cells, CD8 Eff–cancer cells, and B-cells–CD4 Treg) demonstrated positive prognostic impact, while short M2–M1 distances were prognostically unfavorable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is also crucial for diagnostic use.
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| 3. |
- Backman, Max, 1987-, et al.
(författare)
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Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 185, s. 40-52
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial im-mune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163 thorn myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs).Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
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| 4. |
- Bernhard, M., et al.
(författare)
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Institutionalising electoral uncertainty and authoritarian regime survival
- 2020
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Ingår i: European Journal of Political Research. - : Wiley. - 0304-4130 .- 1475-6765. ; 59:2, s. 465-487
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Tidskriftsartikel (refereegranskat)abstract
- Authoritarian incumbents routinely use democratic emulation as a strategy to extend their tenure in power. Yet, there is also evidence that multiparty competition makes electoral authoritarianism more vulnerable to failure. Proceeding from the assumption that the outcomes of authoritarian electoral openings are inherently uncertain, it is argued in this article that the institutionalisation of elections determines whether electoral authoritarianism promotes stability or vulnerability. By 'institutionalisation', it is meant the ability of authoritarian regimes to reduce uncertainty over outcomes as they regularly hold multiparty elections. Using discrete-time event-history models for competing risks, the effects of sequences of multiparty elections on patterns of regime survival and failure in 262 authoritarian regimes from 1946 to 2010 are assessed, conditioned on their degree of competitiveness. The findings suggest that the institutionalisation of electoral uncertainty enhances authoritarian regime survival. However, for competitive electoral authoritarian regimes this entails substantial risk. The first three elections substantially increase the probability of democratisation, with the danger subsequently diminishing. This suggests that convoking multiparty competition is a risky game with potentially high rewards for autocrats who manage to institutionalise elections. Yet, only a small number of authoritarian regimes survive as competitive beyond the first few elections, suggesting that truly competitive authoritarianism is hard to institutionalise. The study thus finds that the question of whether elections are dangerous or stabilising for authoritarianism is dependent on differences between the ability of competitive and hegemonic forms of electoral authoritarianism to reduce electoral uncertainty.
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| 5. |
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| 6. |
- Boese, Vanessa Alexandra, et al.
(författare)
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Deterring Dictatorship: Explaining Democratic Resilience since 1900
- 2020
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Ingår i: SSRN Electronic Journal. - Göteborg : Göteborgs universitet. - 1556-5068.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Democracy is under threat globally from democratically elected leaders engaging in erosion of media freedom, civil society, and the rule of law. What distinguishes democracies that prevail against the forces of autocratization? This article breaks new ground by conceptualizing democratic resilience as a two-stage process, whereby democracies first exhibit resilience by avoiding autocratization altogether and second, by avoiding democratic breakdown given that autocratization has occurred. To model this two-stage process, we introduce the Episodes of Regime Transformation (ERT) dataset tracking autocratization since 1900. These data demonstrate the extraordinary nature of the current wave of autocratization: Fifty-nine (61%) episodes of democratic regression in the ERT began after 1992. Since then, autocratization episodes have killed an unprecedented 36 democratic regimes. Using a selection-model, we simultaneously test for factors that make democracies more prone to experience democratic regression and, given this, factors that explain democratic breakdown. Results from the explanatory analysis suggest that constraints on the executive are positively associated with a reduced risk of autocratization. Once autocratization is ongoing, we find that a long history of democratic institutions, durable judicial constraints on the executive, and more democratic neighbours are factors that make democracy more likely to prevail.
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| 7. |
- Boese, Vanessa Alexandra, et al.
(författare)
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How democracies prevail: democratic resilience as a two-stage process
- 2021
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Ingår i: Democratization. - : Informa UK Limited. - 1351-0347 .- 1743-890X. ; 28:5, s. 885-907
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Tidskriftsartikel (refereegranskat)abstract
- This article introduces a novel conceptualization of democratic resilience - a two-stage process where democracies avoid democratic declines altogether or avert democratic breakdown given that such autocratization is ongoing. Drawing on the Episodes of Regime Transformation (ERT) dataset, we find that democracies have had a high level of resilience to onset of autocratization since 1900. Nevertheless, democratic resilience has become substantially weaker since the end of the Cold War. Fifty-nine episodes of sustained and substantial declines in democratic practices have occurred since 1993, leading to the unprecedented breakdown of 36 democratic regimes. Ominously, we find that once autocratization begins, only one in five democracies manage to avert breakdown. We also analyse which factors are associated with each stage of democratic resilience. The results suggest that democracies are more resilient when strong judicial constraints on the executive are present and democratic institutions were strong in the past. Conversely and adding nuance to the literature, economic development is only associated with resilience to onset of autocratization, not to resilience against breakdown once autocratization has begun.
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| 8. |
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| 9. |
- Edgell, Amanda B, et al.
(författare)
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Establishing Pathways to Democracy Using Domination Analysis
- 2020
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Ingår i: SSRN Electronic Journal. - Göteborg : Göteborgs universitet. - 1556-5068.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- How does the order in which liberalization unfolds affect the likelihood for a successful democratic transition? Dahl was among the first to argue that the sequence matters for the outcome when it comes to democratization. This paper builds upon his work and empirically analyzes pathways to democracy employing the newly developed method of domination analysis. We are the first to demonstrate three key findings: 1) There is a clear structure in terms of order of how most episodes of liberalization from authoritarian rule develop; 2) Such sequences are different in key respects for failed and successful episodes of liberalization; and 3) Clean election elements - in the capacity of electoral management bodies - stand out as developing earlier in episodes that successfully lead to democracy.
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| 10. |
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