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Antitumor activity of T cells often determines treatment efficacy for immunotherapy and radiotherapy. Due to the immunosuppressive tumor microenvironment, tumor-infiltrating T cells often exhibit a hypofunctional exhausted phenotype. Current methods to evaluate T cell exhaustion use flow cytometry or cytokine production measurements that are either destructive to the sample or cannot capture single-cell heterogeneity, respectively. Here, we used fluorescence lifetime imaging of the metabolic co-enzyme NAD(P)H to evaluate T cell metabolism during exhaustion. Exhausted T cells have significantly different NAD(P)H lifetimes compared to functional T cells. This study demonstrates a label-free method to monitor T cell exhaustion in tumors.
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Dan L. Pham, Katherine Mueller, Krishanu Saha, Melissa C. Skala, "Label-free metabolic imaging of tumor-induced T cell exhaustion," Proc. SPIE 11655, Label-free Biomedical Imaging and Sensing (LBIS) 2021, 1165508 (5 March 2021); https://doi.org/10.1117/12.2578763