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

Abstract

ABSTRACTL-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.