Plasmacytoid dendritic cells contribute to doxorubicin-induced tumor arrest in a mouse model of pulmonary metastasis.
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.
Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, Salerno, Italy.
Michela
M
Terlizzi
Ada
A
Popolo
Aldo
A
Pinto
Rosalinda
R
Sorrentino
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000556:secondary; D008546:Melanoma, Experimental; D051379:Mice; D047368:Tumor Burden / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin