Combination therapy with L-arginine and α-PD-L1 antibody boosts immune response against osteosarcoma in immunocompetent mice. Issue 2 (1st February 2017)

• Record Type: Journal Article
• Authors: He, Xiaojun; Lin, Haiqing; Yuan, Li; Li, Binghao
• Is Part Of: Cancer biology & therapy. Volume 18:Issue 2(2017)
• Page Start: 94
• Page End: 100
• Publication Date: 2017-02-01
• Subjects: Combination therapy -- immunotherapy -- L-arginine -- osteosarcoma -- PD-L1; 616.99406
• DOI: 10.1080/15384047.2016.1276136
• Languages: English
• ISSNs: 1538-4047

Abstract

ABSTRACT: L -arginine supplementation was recently proved to promote the function of immune cells, especially T-cells, by facilitating T-cell proliferation, differentiation and survival in vivo . Cytotoxic CD8 + plays a crucial role in modulating anti-cancer response mediated by the immune system, but was restricted by exhaustion. Thus, we hypothesized thatL -arginine, in combination with α-PD-L1 antibody, may provide a favored environment for T-cell response against osteosarcoma. Immunocompetent BALB/c mouse models bearing orthotopic and metastatic osteosarcoma were established to validate this conjecture. We found thatL -arginine significantly elevated the number of splenic CD8 + T-cells, the level of serum interferon-γ, and CD8 + T-cell infiltration. Furthermore, α-PD-L1 antibody protected these amplified CD8 + T-cells from exhaustion, and therefore strengthened the secretion of interferon-γ, granzyme B and perforin by these T-cells. As a result, this combination treatment strategy significantly prolonged survival of osteosarcoma bearing mice, suggesting thatL -arginine supplementation in combination with α-PD-L1 antibody may be a promising method for osteosarcoma patients.