Fluorescent tracking identifies key migratory dendritic cells in the lymph node after radiotherapy

TC Blair, S Bambina, GF Kramer… - Life Science …, 2022 - life-science-alliance.org
TC Blair, S Bambina, GF Kramer, AK Dowdell, AF Alice, JR Baird, AW Lund, BD Piening
Life Science Alliance, 2022life-science-alliance.org
Radiation therapy generates extensive cancer cell death capable of promoting tumor-
specific immunity. Within the tumor, conventional dendritic cells (cDCs) are known to carry
tumor-associated antigens to the draining lymph node (TdLN) where they initiate T-cell
priming. How radiation influences cDC migration is poorly understood. Here, we show that
immunological efficacy of radiation therapy is dependent on cDC migration in
radioimmunogenic tumors. Using photoconvertible mice, we demonstrate that radiation …
Radiation therapy generates extensive cancer cell death capable of promoting tumor-specific immunity. Within the tumor, conventional dendritic cells (cDCs) are known to carry tumor-associated antigens to the draining lymph node (TdLN) where they initiate T-cell priming. How radiation influences cDC migration is poorly understood. Here, we show that immunological efficacy of radiation therapy is dependent on cDC migration in radioimmunogenic tumors. Using photoconvertible mice, we demonstrate that radiation impairs cDC migration to the TdLN in poorly radioimmunogenic tumors. Comparative transcriptional analysis revealed that cDCs in radioimmunogenic tumors express genes associated with activation of endogenous adjuvant signaling pathways when compared with poorly radioimmunogenic tumors. Moreover, an exogenous adjuvant combined with radiation increased the number of migrating cDCs in these poorly radioimmunogenic tumors. Taken together, our data demonstrate that cDC migration play a critical role in the response to radiation therapy.
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