A new microfluidic platform called MIRO has been developed to model the interactions between tumors and their surrounding stromal environments, offering potential solutions for improving immunotherapy effectiveness. Cancer patients often experience varied responses to immunotherapies, with only 20-40% showing significant benefit. Understanding the underlying reasons for this discrepancy is key to advancing treatment protocols.
The research emphasizes the importance of the tumor microenvironment (TME), which affects how immune cells interact with and infiltrate tumors. By recreATING these conditions inside the MIRO platform, scientists are gaining insights how tumor-associated stroma can drive immune exclusion and limit the efficacy of treatments.
Through their work, researchers discovered significant roles played by stromal barriers. "Stromal barriers are associated with immune exclusion and protect cancer cells from antibody-dependent cellular cytotoxicity," stated the study. These barriers hinder immune cell access to tumor cells, making it difficult for treatments like monoclonal antibodies to exert their intended effects.
One of the standout features of MIRO is its ability to dynamically simulate the spatial organization of the tumor-stroma interface, recreATING the conditions found clinically. This model integrates key elements such as cancer-associated fibroblasts (CAFs) and extracellular matrix components, allowing researchers to study immune cell infiltration patterns and responses to treatments effectively.
By employing MIRO, the study found promising results showing how IL2 can combine with anti-HER2 therapies to restore anti-cancer immunity. "IL2 is mainly responsible for the modulation of the migratory behaviour of NK cells," the researchers noted, emphasizing the treatment's role in enhancing immune cell movement and effectiveness against resistant tumors.
Real-time imaging conducted during the experiments revealed increased immune cell activity and velocity upon IL2 treatment. This suggests the potential for leveraging IL2 not only to reactivate dormant immune responses but also to navigate through the dense stromal architecture surrounding cancer cells.
The MIRO model also revealed architectural features similar to those found directly within patient tumors. Specifically, it shows how the structure and organization of ECM and CAFs inform immune activity—insights necessary for patient-centered therapeutic designs.
“MIRO enables the formation of reproducible 2.5D cancer/stroma interface, allowing quantitative studies of immune cell distribution and dynamics upon treatments,” the authors concluded. Such precision could inform clinical strategies targeting both tumors and their microenvironments, potentially enhancing outcomes for patients who currently have limited options.
Moving forward, this innovative approach embodies the promise of personalized medicine by detailing how specific components of the TME impact immune responses. Researchers envision MIRO as not only relevant for HER2+ breast cancer but also adaptable to other cancer types, reflecting the heterogeneous nature of tumors and their associated microenvironments.