In vitro generation of cytotoxic T lymphocyte response using dendritic cell immunotherapy in osteosarcoma

Abstract

Immunotherapy with tumor lysate-pulsed dendritic cells (DCs) is one of the breakthrough strategies used in the treatment of cancer. However, DC-based immunotherapies for osteosarcoma are limited. In the present study, preclinical studies of a C3H osteosarcoma mouse model (produced by subcutaneous injection of LM8 murine osteosarcoma cells) validated the concept that LM8 cell lysate‑pulsed bone marrow‑derived DCs may evoke a more potent immune response compared with DCs that have been matured using polyinosinic:polycytidylic acid (poly I:C). A cytotoxic T lymphocyte (CTL) response was established using two groups of C3H mice (n=9) with osteosarcoma; the treatment group consisted of LM8 cell lysate‑pulsed DCs and the control group consisted of DCs matured using poly I:C. Each group was immunized with doses of 1x106 cells twice per week for 3 weeks. No difference in the expression of cluster of differentiation markers was identified in the two groups. DCs pulsed with LM8 cell lysate were associated with the increased induction of CTL activity. Serum interferon‑γ levels were increased in mice that received DCs pulsed with LM8 cell lysate compared with that in the poly I:C‑matured DC group (P<0.041). Serum interleukin‑4 was decreased in the treatment group vs. the control group (P<0.033). A mixed lymphocyte reaction assay confirmed that LM8‑DC immunotherapy may evoke a significant antigen‑specific immune response in a mouse model. The present study reveals promising data on efficacy of a DC‑based immunotherapy in the treatment of osteosarcoma; however, further clinical studies are warranted.