Neue Wege in der Schweizer Agrarpolitik. Potential von Nachhaltigkeitsbewertungs- Instrumenten zur Verbesserung der Effektivität, Effizienz und Akzeptanz der Schweizer Agrarpolitik

Das Projekt „Neue Wege zur nachhaltigen Landwirtschaft“ wird vom Bundesamt für Landwirtschaft (BLW) mitfinanziert und gemeinsam vom Forschungsinstitut für biologischen Landbau (FIBL), Agroscope und der Hochschule für Agrar-, Forst- und Lebensmittelwissenschaften (HAFL) durchgeführt. Das grundlegende Ziel des Projekts besteht darin zu untersuchen inwieweit betrieblichen Nachhaltigkeitsanalysen genutzt werden können, um die Schweizer Agrarpolitik effektiver, effizienter und bei der Bevölkerung und den Landwirten akzeptierter zu gestalten. Durch das bisherige Direktzahlungssystem haben sich zwar einige unerwünschte Nebeneffekte der landwirtschaftlichen Tätigkeit verringert. Jedoch zeigt sich, dass die Anstrengungen für den Erhalt unserer Lebensgrundlagen noch verstärkt werden müssen. Mit den Reformen der Agrarpolitik und der stärkeren Fokussierung auf die Umweltleistungen und die Umweltschonung ist der administrative Aufwand aus Sicht der Landwirte stetig gestiegen und wird gemeinhin als zu hoch betrachtet. Von daher gilt es Wege zu finden, die das bestehende System vereinfachen, ohne die Ziele grundlegend zu verändern. Gerade kosteneffizient einsetzbare Instrumente, die belastbare, reproduzierbare und kontrollierbare Ergebnisse liefern, könnten bei der Umsetzung im Kontext des Direktzahlungssystems für erhebliche Synergien sorgen und eine Zielerreichung erleichtern. Sie messen einerseits die Leistungen von landwirtschaftlichen Betrieben umfassend und vergleichbar und verifizieren gleichzeitig die Plausibilität der Angaben auf kosteneffektive Art und Weise. Dabei können Aspekte der betrieblichen Beratung sinnvoll und umfassend mit einem Direktzahlungssystem integriert werden. Auf Grundlage einer ausführlichen Betrachtung bestehender Nachhaltigkeits-bewertungsverfahren, der Auswertung relevanter Tools und Indikatorensets und Feedback aus Gesprächen mit dem BLW und ausgewählten Experten wurde ein zielgerichtetes Konzept ausgearbeitet. Dieses besteht aus zwei eng miteinander verbundenen Komponenten, die beide auf einer fundierten Nachhaltigkeitsanalyse aufbauen: (1) Eine umfassende Nachhaltigkeitsplanung, welche einen nachhaltigen Betriebsentwicklungsprozess fördert; Und (2) ein klar definiertes Punktesystem, welches wirtschaftliche Anreize zur Nachhaltigkeit in der Form von Direktzahlungen setzt. Eine vom Projektteam vorgenommene Evaluierung der Ausgestaltung der zwei Komponenten hat daraufhin ergeben, dass vier konkrete Handlungsoptionen in einem nächsten Schritt erprobt werden sollten. Diese beinhalten finanzielle Anreize zur Erstellung eines betrieblichen Nachhaltigkeitsplans und Indikatorensets, die einen unterschiedlichen Umfang besitzen. Der Nachhaltigkeitsplan kann dabei die Nachhaltigkeitsziele definieren und als Basis für die Punktevergabe dienen

Towards an operational framework for farm sustainability assessment and payment allocation under the CAP

European Common Agricultural Policy (CAP) moved from production to income support and protecting the environment (e.g. AEMs). Global challenges (ecological, social, economic) requires a fundamental overhaul of the CAP to a holistic, consistent, efficient and fair mechanism rooted in sustainability

Assessing the Sustainability Performance of Organic and Low-Input Conventional Farms from Eastern Poland with the RISE Indicator System

The aim of this study was to examine the sustainability performance of organic and low-input conventional farms with the sustainability assessment tool—RISE 3.0. It is an indicator-based method for holistic assessment of sustainability of agricultural production at farm level. Ten organic and 10 conventional farms from eastern Poland, Lublin province were assessed. According to the thresholds levels of the RISE method, organic farms performed positively for 7 out of 10 themes, while the values of the other 3 topics, biodiversity, working conditions, and economic viability, were at medium level. Conventional farms reached positive scores for 9 out of 10 themes. The only middle-performing theme was biodiversity. None of the two farm types had the lowest, problematic scores for examined themes. For the theme biodiversity and two indicators (greenhouse gas balance and intensity of agricultural production), significant differences between farming systems were found. Biodiversity performance, an important indicator of sustainability, estimated with the RISE system, was highly correlated with measured on-field weed flora and Orthoptera biodiversity of farms. High soil acidity and low crop productivity, improper weed regulation, and energy management were the most common problems in both types of farms. Working hours and wage and income levels were also assessed as being low. Recommendations to improve the sustainability of both organic and conventional farms are presented

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

BACKGROUND Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. METHODS In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. FINDINGS When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. CONCLUSIONS We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. FUNDING This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen

RISE- Response-inducing sustainability evaluation

RISE is a computer-supported indicator-based method for assessing the economic, social and environmental sustainability performance of agricultural production at the farm level. The purpose of RISE is to contribute to enhancing the sustainability of agricultural production, by supporting knowledge-based processes that are founded on voluntary participation, confidentiality and capacity building. The evaluation is based on ten indicators that reflect environmental, economic and social aspects. The most important data source is a questionnaire-based interview with the farmer. The evaluated data are visualized as a sustainability polygon and serve as a basis to a feedback dialogue in which the farmer and the trained RISE consultant jointly identify potentials for improving farm sustainability performance. Training in the RISE method for professionals in the agriculture and related industries are regularly carried out. On completion of the course, participants are able to use the RISE method independently to evaluate the sustainability of agricultural operations. RISE is aimed at agricultural consultants, for use in education, in development projects and in raw material sourcing. The tool is internationally relevant for all farms, organic and conventional. The software has been tested around the world, is available in seven languages and can be used both on- and off-line

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T$_{H}$)1 and T$_{H}$17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T$_{H}$17 cells imprinted in the intestine by a commensal Bacteroides species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated Bacteroides-specific CD4$^{+}$ T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T-H)1 and T(H)17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T(H)17 cells imprinted in the intestine by a commensal Bacteroides species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated Bacteroides-specific CD4(+) T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Berner, Fiamma. Medical Research Center; SuizaFil: Friebel, Ekaterina. Universitat Zurich; SuizaFil: Unger, Susanne. Universitat Zurich; SuizaFil: Wyss, Nina. Kantonsspital St. Gallen; Suiza. Medical Research Center; SuizaFil: Martinez Gomez, Julia. Universitat Zurich; SuizaFil: Purde, Mette Triin. Medical Research Center; SuizaFil: Niederer, Rebekka. Medical Research Center; Suiza. Kantonsspital St. Gallen; SuizaFil: Porsch, Maximilian. Kantonsspital St. Gallen; SuizaFil: Lichtensteiger, Christa. Kantonsspital St. Gallen; SuizaFil: Kramer, Rafaela. Universitat Erlangen-Nuremberg; AlemaniaFil: Erdmann, Michael. Universitat Erlangen-Nuremberg; AlemaniaFil: Schmitt, Christina. Ludwig Maximilians Universitat; AlemaniaFil: Heinzerling, Lucie. Ludwig Maximilians Universitat; Alemania. Universitat Erlangen-Nuremberg; AlemaniaFil: Abdou, Marie Therese. Kantonsspital St Gallen; SuizaFil: Karbach, Julia. Krankenhaus Nordwest; AlemaniaFil: Schadendorf, Dirk. German Cancer Research Center; AlemaniaFil: Zimmer, Lisa. German Cancer Research Center; AlemaniaFil: Ugurel, Selma. German Cancer Research Center; AlemaniaFil: Klümper, Niklas. Universitat Bonn; AlemaniaFil: Hölzel, Michael. Universitat Bonn; AlemaniaFil: Power, Laura. Universitat Zurich; SuizaFil: Kreutmair, Stefanie. Universitat Zurich; SuizaFil: Capone, Mariaelena. Istituto Nazionale Tumori; ItaliaFil: Madonna, Gabriele. Istituto Nazionale Tumori; ItaliaFil: Cevhertas, Lacin. Bursa Uludag University; Turquía. Universitat Zurich; SuizaFil: Heider, Anja. Universitat Zurich; SuizaFil: Amaral, Teresa. University Hospital Tübingen; Alemania. Eberhard Karls Universität Tübingen; AlemaniaFil: Hasan Ali, Omar. University of British Columbia; Canadá. Kantonsspital St Gallen; Suiza. Universitat Zurich; SuizaFil: Bomze, David. Kantonsspital St Gallen; Suiza. Tel Aviv University; Israe

Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade.

Cancer treatment with immune checkpoint blockade (ICB) often induces immune-related adverse events (irAEs). We hypothesized that proteins coexpressed in tumors and normal cells could be antigenic targets in irAEs and herein described DITAS (discovery of tumor-associated self-antigens) for their identification. DITAS computed transcriptional similarity between lung tumors and healthy lung tissue based on single-sample gene set enrichment analysis. This identified 10 lung tissue-specific genes highly expressed in the lung tumors. Computational analysis was combined with functional T cell assays and single-cell RNA sequencing of the antigen-specific T cells to validate the lung tumor self-antigens. In patients with non-small cell lung cancer (NSCLC) treated with ICB, napsin A was a self-antigen that elicited strong CD8+ T cell responses, with ICB responders harboring higher frequencies of these CD8+ T cells compared with nonresponders. Human leukocyte antigen (HLA) class I ligands derived from napsin A were present in human lung tumors and in nontumor lung tissues, and napsin A tetramers confirmed the presence of napsin A-specific CD8+ T cells in blood and tumors of patients with NSCLC. Napsin A-specific T cell clonotypes were enriched in lung tumors and ICB-induced inflammatory lung lesions and could kill immortalized HLA-matched NSCLC cells ex vivo. Single-cell RNA sequencing revealed that these T cell clonotypes expressed proinflammatory cytokines and cytotoxic markers. Thus, DITAS successfully identified self-antigens, including napsin A, that likely mediate effective antitumor T cell responses in NSCLC and may simultaneously underpin lung irAEs