1. Microfluidics guided by deep learning for cancer immunotherapy screening
- Author
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Zheng Ao, Hongwei Cai, Zhuhao Wu, Liya Hu, Asael Nunez, Zhuolong Zhou, Hongcheng Liu, Maria Bondesson, Xiongbin Lu, Xin Lu, Ming Dao, and Feng Guo
- Subjects
Deep Learning ,Lymphocytes, Tumor-Infiltrating ,Multidisciplinary ,Neoplasms ,Microfluidics ,Tumor Microenvironment ,Humans ,Immunologic Factors ,Immunotherapy ,Early Detection of Cancer - Abstract
Immunocyte infiltration and cytotoxicity play critical roles in both inflammation and immunotherapy. However, current cancer immunotherapy screening methods overlook the capacity of the T cells to penetrate the tumor stroma, thereby significantly limiting the development of effective treatments for solid tumors. Here, we present an automated high-throughput microfluidic platform for simultaneous tracking of the dynamics of T cell infiltration and cytotoxicity within the 3D tumor cultures with a tunable stromal makeup. By recourse to a clinical tumor-infiltrating lymphocyte (TIL) score analyzer, which is based on a clinical data-driven deep learning method, our platform can evaluate the efficacy of each treatment based on the scoring of T cell infiltration patterns. By screening a drug library using this technology, we identified an epigenetic drug (lysine-specific histone demethylase 1 inhibitor, LSD1i) that effectively promoted T cell tumor infiltration and enhanced treatment efficacy in combination with an immune checkpoint inhibitor (anti-PD1) in vivo. We demonstrated an automated system and strategy for screening immunocyte-solid tumor interactions, enabling the discovery of immuno- and combination therapies.
- Published
- 2022