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- W4313351782 abstract "Abstract T-regulatory cells (Tregs) create an immunosuppressive environment that reduces the efficacy of anti-tumor immunotherapy. Depletion of Tregs enhances anti-tumor immune responses, but also affects T-effector cells. Previously we showed that blockade of chemokine ligand 1 (CCL1) inhibits Treg conversion, their suppressive function, and in combination with intra-tumoral CpG-ODN results in complete rejection of tumors in BALB-NeuT tolerant mice. Most importantly, this therapeutic combination does not affect T-effector function and increases tumor-lytic CD8+NKG2D+ cells within the tumor. Here we expand on the role of blocking CCL1 in enhancing anti-tumor immunotherapy. Using CCL1 knockout (CCL1ko) mice, we found no impairment in TGFβ dependent de novo Treg conversion, however CCL1ko Tregs are less suppressive in vitro, than their wild type counterparts. CCL1ko mice treated with intratumoral CpG showed a marked reduction in tumor growth and a significant increase in tumor rejection as compared to similarly treated C57b control mice. Examination of lymphocyte populations within B16 and MucI tumors showed elevated levels of CD8+ cells. Finally the evaluation of levels of intra-tumoral cytokines and chemokines revealed elevated levels of IFNγ, CXCL9, CCL3 and CXCL10 in tumors grown in CCL1ko mice, suggesting a pro-inflammatory environment. Taken together these data support the role of CCL1as a critical factor for the maintenance of the suppressive function of Tregs." @default.
- W4313351782 created "2023-01-06" @default.
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- W4313351782 date "2011-04-01" @default.
- W4313351782 modified "2023-09-23" @default.
- W4313351782 title "Critical function of CCL1 in the maintenance of T regulatory cell’s suppressive role. (66.14)" @default.
- W4313351782 doi "https://doi.org/10.4049/jimmunol.186.supp.66.14" @default.
- W4313351782 hasPublicationYear "2011" @default.
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