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

Abstract

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.

Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help

“…34 . Kaede transgenic mice were crossed with CCR7 −/− mice in house to generate Kaede CCR7 −/− animals as previously described 67 .…”

“…Tumor processing. Tumor processing was performed as recently described 67 . Briefly, following dissection into small fragments, tumors were transferred into C tubes from Miltenyi Biotec containing enzyme digest mix with 250U/mL collagenase IV (Worthington Biochemical, #LS004188), 30U/mL DNase I (Millipore-Sigma, #4536282001), 5 mM CaCl 2 , 5% heat inactivated FBS and HBSS.…”

Radiation-induced tumor immune microenvironments and potential targets for combination therapy

“…Conventional type I dendritic cells (CD103 + cDC1) cross-presented antigens on MHC class I to CD8 + T cells, recruited T cells to the tumor by producing CXCL9 and CXCL10 and produced IL-12 after sensing IFN-γ released from T cells, 59 , 60 leading to the initiation and maintenance of antitumor immunity and increasing antitumor immunity in a mouse model, while CD11b + cDC2s specifically primed CD4 + T cells and were heterogeneous. 61 , 62 mregDCs are a recently discovered subtype of DCs. They are derived from DC1s and DC2s, and their differentiation is associated with the uptake of tumor antigens by DC1s and DC2s.…”

Biomimetic nanoparticles for DC vaccination: a versatile approach to boost cancer immunotherapy

“…DCs in lymph nodes are also a viable target for vaccines, and if antigens and adjuvants are delivered to lymph nodes, vaccines can also produce anti-tumor immune effects. 159 For DCs in lymph nodes, biomolecular ligands may not be needed because they are abundant in lymph nodes and still have phagocytic activity. The particle size is inversely proportional to the absorption efficiency of DCs.…”