[Mechanism of augmented anti-tumor immunity in reconstituted lymphopenic mice immunized with melanoma vaccine].
OBJECTIVE
To explore mechanisms of the augmented anti-tumor immunity observed in reconstituted lymphopenic mice (RLM) receiving melanoma vaccination.


METHODS
The study is to investigate the anti-tumor immunity of tumor vaccination during early immune reconstitution period following irradiation and cyclophosphamide (CY)-induced lymphopenia. Lymphopenic mice were subsequently reconstituted with naive splenocytes from syngeneic mice and immunized with irradiated melanoma cells F10 (irradiation experiment) and GM-CSF-modified D5 melanoma cells (D5-G6) (CY experiment). Controls included normal C57BL/6 mice receiving the corresponding vaccination, un-immunized naive mice and RLM. 8 - 10 days after vaccination, tumor vaccine draining lymph nodes (TVDLN) were harvested and phenotyped by FACS analysis. T cells purified from TVDLN were stimulated with anti-CD3 and anti-TCRbeta and proliferation was assessed by [(3)H]-TdR incorporation and FACS assay was performed for CD69 expression.


RESULTS
The augmented anti-tumor immunity correlated with a significant increase in the percentage of T cells with activation/memory phenotype in the TVDLN of vaccinated RLM, compared to that of the controls. There was also a significant increase in the density of DCs in TVDLNs. The activation threshold of T cells generated from vaccinated RLM was significantly decreased, resulting in markedly enhanced proliferating capability upon anti-CD3 stimulation.


CONCLUSIONS
This study suggests that the augmented anti-tumor immunity observed in vaccinated RLM is due to down regulated activation threshold of T cells during lymphopenia-driven T cell proliferation, which may in turn facilitate the breaking down of immune tolerance to weak tumor antigens upon vaccination with tumor cell vaccines.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute for Cancer Research, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an, 710061, China.
Jun
J
Ma
Yi-li
YL
Wang
Hong-ming
HM
Hu
Bernard A
BA
Fox
Lü-sheng
LS
Si
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003520:Cyclophosphamide; D008198:Lymph Nodes / Q000276:immunology; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014916:Whole-Body Irradiation
D019496:Cancer Vaccines; D003520:Cyclophosphamide