The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector.
To explore the anti-tumor effect and immune mechanism mediated by a new recombinant adeno-associated virus (rAAV) encoding secondary lymphoid tissue chemokine (SLC) mature peptide gene. AAV Helper-Free system was used for rAAV-SLC package. The anti-tumor effect of SLC was detected by bearing tumor established from Hepal-6 cells both in C57BL/6J and nude mice. Flow cytometry analysis and IHC for Tumor-infiltrating T cells and CD11c+DCs were also investigated to explore the immunological mechanism. rAAV-SLC was successfully packaged in AAV293 cells and transfected Hepal-6 tumor cells at high efficiency. The anti-tumor effect was demonstrated by less tumor weight and longer survival outcome. Coincident with the anti-tumor response, local elaboration of SLC within the tumor bed elicited a heavy infiltration of CD4+, CD8+T cells and CD11c+ dendritic cells into the tumor sites. More importantly, there was higher infiltration of Foxp3+ regulatory T cells (Tregs). Local elaboration of SLC mediated by rAAV-SLC has strong T cell mediated anti-tumor effect. The study also suggested that Tregs in the tumor microenvironment tampered the anti-tumor effect.
Rilun
R
Li
Heng
H
Hu
Huiying
H
Ma
Long
L
Chen
Binbin
B
Zhou
Yinkun
Y
Liu
Chunmin
C
Liang
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D000229:Dependovirus / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism*; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014161:Transduction, Genetic
D000970:Antineoplastic Agents; D054421:Chemokine CCL21; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit