The biology of plasmacytoid dendritic cells (pDCs) in
tumors is an emerging area of investigation. pDCs populate many human solid
tumors, including
lung cancer. The aim of our study was to understand the role of pDCs in pulmonary
metastases during the treatment with conventional
antitumor agents. For this purpose, C57Bl/6 mice were inoculated with the metastatic cell line B16-F10 or B16-Flt3L cells. The administration of
doxorubicin significantly reduced the amount of pulmonary
metastases in both experimental models. It is interesting to note that, 5 hours after injection,
doxorubicin-induced
tumor cell death was associated with higher influx of pDCs to the lung, which at 24 hours populated the mediastinal lymph nodes. In this context, lung
tumor-derived pDCs obtained from mice treated with
doxorubicin had higher levels of MHC I and MHC II that well correlated with the higher proliferation rate of CD4 and CD8 T cells, compared with PBS mice.
Siglec-H and PD-L1 levels were not altered on lung
tumor-associated pDCs derived from
doxorubicin-treated and PBS-treated mice. In addition, lung
tumor-associated pDCs obtained from mice treated with
doxorubicin released higher levels of
granzyme B. The administration of 2 consecutive doses of
doxorubicin in lung
tumor-bearing mice showed that B16-Flt3L-implanted mice had lower
tumor burden than B16-F10-implanted mice. In conclusion, our data highlight the crucial role of the proinflammatory pDCs for the adaptive antitumor immunity. Strategies aiming at modulating pDC phenotype and activity in the
tumor site might prove to be novel and effective, enhancing the conventional/actual antitumor strategies.