Whole-body bioluminescence imaging of T-cell response in PDAC models

Roisin McMorrow, Giorgia Zambito, Alex Nigg, Karishma Lila, Thierry P. P. van den Bosch, Clemens W. G. M. Lowik,Laura Mezzanotte

Frontiers in Immunology(2023)

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摘要
IntroductionThe location of T-cells during tumor progression and treatment provides crucial information in predicting the response in vivo. MethodsHere, we investigated, using our bioluminescent, dual color, T-cell reporter mouse, termed TbiLuc, T-cell location and function during murine PDAC tumor growth and checkpoint blockade treatment with anti-PD-1 and anti-CTLA-4. Using this model, we could visualize T-cell location and function in the tumor and the surrounding tumor microenvironment longitudinally. We used murine PDAC clones that formed in vivo tumors with either high T-cell infiltration (immunologically 'hot') or low T-cell infiltration (immunologically 'cold'). ResultsDifferences in total T-cell bioluminescence could be seen between the 'hot' and 'cold' tumors in the TbiLuc mice. During checkpoint blockade treatment we could see in the tumor-draining lymph nodes an increase in bioluminescence on day 7 after treatment. ConclusionsIn the current work, we showed that the TbiLuc mice can be used to monitor T-cell location and function during tumor growth and treatment.
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关键词
bioluminescence imaging (BLI),T-cell activation,PDAC,pancreatic ductal adenocarcinoma,immune checkpoint inhibitors (ICI),tumor microenvironment (TME),tumor-draining lymph nodes (TDLN)
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