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Cancer Biol Ther. 2017 Feb;18(2):94-100. doi: 10.1080/15384047.2016.1276136. Epub 2017 Jan 3.

Combination therapy with L-arginine and α-PD-L1 antibody boosts immune response against osteosarcoma in immunocompetent mice.

Author information

1
a Department of Orothopaedics , The Second Hospital of Jiaxing, The Second Affiliated Hospital of Jiaxing University , Jiaxing , China.
2
b Department of Epidemiology , School of Public Health, Fudan University , Shanghai , China.
3
c Department of Orothopaedics , Institute of Orthopaedic Research, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou , China.

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 that L-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 that L-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 that L-arginine supplementation in combination with α-PD-L1 antibody may be a promising method for osteosarcoma patients.

KEYWORDS:

Combination therapy; L-arginine; PD-L1; immunotherapy; osteosarcoma

PMID:
28045576
PMCID:
PMC5362985
DOI:
10.1080/15384047.2016.1276136
[Indexed for MEDLINE]
Free PMC Article

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