4.6 Article

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

Journal

LIFE SCIENCE ALLIANCE
Volume 5, Issue 9, Pages -

Publisher

LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202101337

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Funding

  1. National Institutes of Health (NIH) [R01CA182311, R01 CA244142]
  2. NIH [R01CA208644]
  3. Providence Foundations of Oregon

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This study demonstrates that the immunological efficacy of radiation therapy depends on cDC migration in radioimmunogenic tumors. Furthermore, the combination of an exogenous adjuvant with radiation therapy can increase the migration of cDCs in poorly radioimmunogenic tumors.
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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