CCL19 reduces tumour burden in a model of advanced lung cancer.
Epstein-Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To mimic therapy in late-stage disease, 3-month-old transgenic mice were treated with recombinant CCL19 (0.5 microg dose(-1)) by intranodal (axillary lymph node region) injection three times per week for 4 weeks. CCL19 treatment led to a marked reduction in tumour burden with extensive mononuclear infiltration of the tumours compared to diluent treated controls. Flow cytometric analyses showed significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-beta. Our findings show that CCL19 may serve as a potential immune stimulator and provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy.
Hillinger
S
S
Thoracic Surgery, University Hospital Zürich, Zürich, Switzerland. sven.hillinger@usz.ch
Yang
S-C
SC
Batra
R K
RK
Strieter
R M
RM
Weder
W
W
Dubinett
S M
SM
Sharma
S
S
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic
C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC