Osteosarcoma is the most common primary bone
tumor in both humans and dogs. It is a highly metastatic
cancer and
therapy has not improved significantly since the inclusion of
adjuvant chemotherapy into disease treatment strategies.
Osteosarcoma is an immunogenic
tumor, and thus development of
immunotherapies for its treatment, especially treatment of microscopic pulmonary
metastases might improve outcomes. NK cells are lymphocytes of the innate immune system and can recognize a variety of stressed cells, including
cancer cells, in the absence of major histocompatibility complex (MHC)-restricted receptor
ligand interactions. NK cells have a role in controlling
tumor progression and
metastasis and are important mediators of different therapeutic interventions. The core hypothesis of adoptive natural killer (NK) cell
therapy is there exists a natural defect in innate immunity (a combination of
cancer-induced reduction in NK cell numbers and immunosuppressive mechanisms resulting in suppressed function) that can be restored by adoptive transfer of NK cells. Here, we review the rationale for adoptive NK cell
immunotherapy, NK cell biology, TGFβ and the immunosuppressive microenvironment in
osteosarcoma, manufacturing of ex vivo expanded NK cells for the dog and provide perspective on the present and future clinical applications of adoptive NK cell
immunotherapy in spontaneous
osteosarcoma and other
cancers in the dog.