title: Combination therapy with L-arginine and α-PD-L1 antibody boosts immune response against osteosarcoma in immunocompetent mice.
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.
authors.affiliation: a Department of Orothopaedics , The Second Hospital of Jiaxing, The Second Affiliated Hospital of Jiaxing University , Jiaxing , China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: He
authors.affiliation: a Department of Orothopaedics , The Second Hospital of Jiaxing, The Second Affiliated Hospital of Jiaxing University , Jiaxing , China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Lin
authors.affiliation: b Department of Epidemiology , School of Public Health, Fudan University , Shanghai , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: c Department of Orothopaedics , Institute of Orthopaedic Research, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Binghao
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D001120:Arginine; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D001120:Arginine
keywords: Combination therapy; L-arginine; PD-L1; immunotherapy; osteosarcoma