Burkhard, B. | bioRxiv Science

bioRxiv2025

Memory CD4 T cells orchestrate neoadjuvant-responsive niches in colorectal cancer liver metastases

Colorectal cancer frequently progresses to liver metastases (CRLM), a stage with limited treatment options and poor prognosis. Neoadjuvant chemotherapy is used to control tumor growth and enable resection, yet many patients fail to respond, and the mechanisms underlying this variability remain unclear. To identify determinants of treatment response, we profiled T cell states and their spatial organization in CRLM. We found that spatial arrangement and polarization of CD4 memory T cell networks determine treatment outcome. In responders, Th1-like CD4 memory T cells organized with effector-memory CD8 T cells and antigen-presenting cells (APCs) into therapy-responsive immune niches (TRINs) that support CD4-mediated APC licensing and local immune engagement. Non-responders lacked such immune architecture, exhibiting myeloid-rich regions dominated by circulating-like CD4 memory and regulatory T cells. CD4-driven TRINs thus emerge as key determinants of chemotherapy efficacy and provide a rationale for developing biomarkers and strategies that enhance CD4-APC-CD8 crosstalk within organized immune niches. Statement of significanceTh1-polarized CD4 memory T cells form therapy-responsive immune niches (TRINs) that orchestrate CD4, CD8, and APC function in colorectal cancer liver metastases, a clinically challenging and immunologically cold tumor type. TRINs define chemotherapy response and provide a mechanistic foundation for biomarker development and immunotherapy strategies designed to restore anti-tumor immunity.

immunology↗

bioRxiv2020

Assessment of the relationships between agroecosystem condition and soil erosion regulating ecosystem service in Northern Germany

Ecosystems provide multiple services that are necessary to maintain human life and activities. Agroecosystems are very productive suppliers of biomass-related provisioning ecosystem services, e.g. food, fibre and energy. At the same time, they are highly dependent on respective ecosystem condition and regulating ecosystem services such as soil fertility, water supply or soil erosion regulation. Assessments of this interplay of ecosystem conditions and services are very important to understand the relationships in highly managed systems. Therefore, the aim of this study is twofold: First, to test the concept and indicators proposed by the European Union Working Group on Mapping and Assessment of Ecosystems and their Services (MAES) for the assessment of agroecosystem condition at a regional level. Second, to identify the relationships between ecosystem condition and the delivery of ecosystem services. For this purpose, we applied an operational framework for integrated mapping and assessment of ecosystems and their services. We used the proposed indicators to assess the condition of agroecosystems in Northern Germany and the provision of the regulating ecosystem service control of erosion rates. We used existing data that are available from official databases for the calculation of the different indicators. We show maps of environmental pressures, ecosystem condition and ecosystem service indicators for the Federal State of Lower Saxony. Furthermore, we identified areas within the state where pressures are high, conditions are limited, and more sustainable management practices are needed. Despite the limitations of the indicators and data availability, our results show positive, negative and no significant correlations between the different pressures and condition indicators, and the control of erosion rates. Although the idea behind the MAES framework is to show the general condition of an ecosystem, when looking at the relationships between condition and ecosystem services, we identified that not all the indicators - as they are proposed- are suitable to explain to what extent ecosystems are able to provide certain ecosystem services. Further research on other ecosystem services provided by agroecosystems would facilitate the identification of synergies and trade-offs. Moreover, the definition of a reference condition, although complicated for anthropogenically highly modified agroecosystems, would provide a benchmark to compare information on the condition of the ecosystems, leading to better land use policy and management decisions

ecology↗