![]() By quantifying the release of radioactive materials such as 51Chromium or fluorescence dyes such as Calcein preloaded in tumor cells, or the incorporation of fluorescence dyes such as propidium iodide (PI) into the dead tumor cells, immune cell-mediated tumor cell death is measured ( 8, 9). Standard cytotoxic assays are performed by mixing immune cells and tumor cells in test tubes or round-bottomed well plates, and measuring tumor cell death within them. One of the most critical assays to develop immune cells for ACT-based cancer treatment is the cytotoxicity assay, which measures the ability of immune cells to kill tumor cells. In addition, CAR-T cell therapy has been successful for B cell-originated blood cancers such as leukemia, lymphoma, and multiple myeloma, but its application for solid tumors has not been straightforward ( 7). While genome editing tools are applied to T cells to minimize allogeneic immune responses ( 5), other subsets of lymphocytes such as natural killer (NK) cells that efficiently kill tumor cells but exhibit minimal adverse effects in allogeneic settings are considered to develop allogeneic off-the-shelf immune cell therapeutics ( 6). For example, T cells from cancer patients must be used to prepare CAR-T cells because T cells from donors can cause severe allogeneic immune responses, necessitating weeks of manufacturing time and high manufacturing expenses ( 4). While CAR-T cell therapy has been tremendously successful in clinical trials and is now being used to treat refractory cancer patients, it still faces a number of challenges ( 3). Additionally, NK cells and T cells in FN-coated microwells exhibited divergent dynamic behaviors, indicating that two distinct subsets of cytotoxic lymphocytes respond differentially to extracellular adhesion cues during target cell recognition.Īdoptive cell therapy (ACT) using ex vivo cultured/engineered immune cells is an emerging therapy for cancer treatment since the recent success of chimeric antigen receptor (CAR) T cell therapy ( 1, 2). Both natural killer (NK) cells and T cells showed higher cytotoxicity against round tumor cells in BSA-coated microwells compared to flat tumor cells in FN-coated microwells, suggesting that extracellular adhesion-mediated firm adhesion of tumor cells made them more resistant to immune cell-mediated killing. The seeding densities of solid tumor cells and immune cells were tuned to maximize one-to-one pairing within a single microwell, and live cell imaging was performed to examine dynamic cell-cell interactions and immune cell cytotoxicity at a single cell level. Solid tumor cells in bovine serum albumin (BSA)-coated microwells did not attach to the surfaces and exhibited a round morphology, but solid tumor cells in fibronectin (FN)-coated microwells adhered firmed to the substrates with a flat shape. In this study, we sought to determine the effects of extracellular adhesion provided by extracellular matrix (ECM) of TME on immune cell cytotoxicity by devising microwell arrays coated with proteins either preventing or promoting cell adhesion. ![]() To improve ACT for solid tumors, it is crucial to comprehend how the numerous components of the tumor microenvironment (TME) surrounding solid tumor cells influence killing ability of immune cells. ![]() 3Department of Materials Science and Engineering, Research Institute of Advanced Materials, Institute of Engineering Research, Bio-MAX Institute, Soft Foundry Institute, Seoul National University, Seoul, South KoreaĪdoptive cell therapy (ACT) using ex vivo engineered/expanded immune cells demonstrated poor efficacy against solid tumors, despite its great success in treating various hematopoietic malignancies.2Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea.1Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, South Korea.Seong-Eun Kim 1 Suji Yun 2 Junsang Doh 2,3* ![]()
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