The project, led by Dr. Anne Régnier‑Vigouroux of Johannes Gutenberg University Mainz, investigated the cytokine IL‑38 as a novel immunomodulator in the tumor microenvironment of glioblastoma. The consortium, coordinated by Prof. Javier Mora Rodríguez of Universidad Costa Rica, also included Prof. Rodrigo Mora, Prof. Steve Quiros, Prof. Warner Alpizar, Dr. Carsten Geiß, and Dr. Elvira Salas. Funding was provided by the German Federal Ministry of Education and Research (BMBF). The collaboration began in early 2019 and culminated in a final symposium held in February 2023, with key milestones and workshops in San José, Costa Rica, and Mainz, Germany.

Experimentally, the team generated IL‑38 knockout glioblastoma cell lines using CRISPR‑Cas technology. Reagents for the knockout and the creation of stable histone‑H2B‑GFP reporter lines were produced, and the knockout was validated by measuring IL‑38 levels in both cell lysates and conditioned media. Parallel work established a spheroid culture system employing the murine SMA‑560 and human NCH82 glioblastoma cell lines, allowing the assessment of IL‑38 expression and cell‑death markers in a three‑dimensional context. In vitro assays revealed that neutralising anti‑IL‑38 antibodies could modulate tumor cell viability, although the results were not yet definitive. In vivo studies, conducted in a mouse glioblastoma model, showed promising indications that IL‑38 deficiency or blockade may influence tumor growth and immune infiltration, suggesting a potential therapeutic angle.

Complementary to the wet‑lab work, an in‑silico approach was undertaken using the BioNetUCR platform developed by Prof. Rodrigo Mora. This computational framework identified two transcription factors and one microRNA that regulate IL‑38 expression. Dr. Geiß extended this analysis to search for IL‑38‑related receptors and transporters, employing BioNetUCR and the COPASI modelling tool. These bioinformatics findings provide a mechanistic basis for the observed phenotypes and guide future experimental designs.

Despite the technical progress, the project faced significant logistical challenges. Several planned visits between German and Costa Rican laboratories were cancelled due to insufficient funding from the Costa Rican ministry and later by the COVID‑19 pandemic. Consequently, in‑vitro experiments in San José were delayed, and planned analyses of glioblastoma patient samples, originally slated for 2020, were postponed and ultimately removed from the work programme in 2021. The in‑vitro data remained inconclusive, whereas the in‑vivo results were considered more promising, prompting a shift in focus toward animal studies and the refinement of the spheroid system.

The consortium’s collaborative framework was established through an opening workshop in February 2019, where laboratory tours, scientific discussions, and the definition of experimental timelines were conducted. Subsequent meetings, including a second workshop in Mainz in July 2020 and the final symposium in February 2023, served to update progress, present findings, and plan future directions. The project’s outcomes include the generation of IL‑38 knockout cell lines, a validated spheroid model, preliminary in‑vivo evidence of IL‑38’s role in glioblastoma, and a computational model linking IL‑38 to specific transcription factors and microRNAs. These results lay the groundwork for further investigations into IL‑38 as a therapeutic target and demonstrate the feasibility of a sustained international research partnership despite funding and pandemic‑related setbacks.