Microdroplet-engineered organoids and immune microenvironment construction

Solid tumor immunotherapy is challenged by immunosuppressive tumor microenvironments and limited tumor-specific T-cell responses. Here, we developed a high-throughput droplet-engineered organoid (DEO) platform to enable both immunotherapy discovery and personalized T-cell generation. DEOs preserve key tumor and immune characteristics, providing a physiologically relevant platform to investigate tumor–immune interactions. Using this system, we identified ROCK signaling as a regulator of antitumor immunity and demonstrated that ROCK activation enhances T-cell infiltration and cytotoxicity, with potential to improve checkpoint immunotherapy. Furthermore, physically inactivated patient-derived organoids were used as personalized tumor antigen sources to efficiently enrich tumor-reactive T cells from peripheral blood while preserving broad tumor antigen recognition. Together, these studies establish engineered tumor organoids as a versatile platform bridging tumor–immune modeling, therapeutic discovery, and personalized T-cell manufacturing, offering a new strategy for precision immunotherapy of solid tumors.

Dr. Shaohua Ma received his B.Eng from the Department of Polymer Materials and Engineering at Sun Yat-sen University in 2009, and Ph.D. from the Department of Chemistry at the University of Cambridge in 2013. He did the postdoctoral training at the University of Oxford in 2013 – 2017 before joining Tsinghua University in 2017, first as an assistant professor and then associate professor (core-PI) at Tsinghua-Berkeley Shenzhen Institute (TBSI). He is now an associate professor with tenure at Institute of Biopharmaceutical and Health Engineering (iBHE), Tsinghua Shenzhen International Graduate School (SIGS). His research interests include intelligent microfluidics, organoids and stem cell engineering, organs-on-a-chip, 3D bioprinting, and has contributed over 80 papers as the first and corresponding authors to these fields.