A Review of T-Cell Related Therapy for Osteosarcoma

Abstract

Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.

Keywords: T-cell; immunotherapy; osteosarcoma.

Figure 1

The three phases of cancer immunoediting. The tumor is gradually edited to gain resistance to immune attack. (a) In the Elimination phase, the tumor is eliminated by the immune attack. (b) In the Equilibrium phase, some of the edited tumor cells survive and are eliminated incompletely. (c) In the Escape phase, highly edited tumor cells can proliferate. The apparent clinical cancer is in the Escape phase.

Figure 2

The two main methods of dendritic cell (DC) vaccine. The ex vivo DC vaccine uses the method of adoptive immunotherapy. The in vivo DC vaccine uses a specific antibody conjunction with an antigen that targets DCs and activates T-cells via cross presentation.

Figure 3

The development of chimeric antigen receptor (CAR) T-cells. A CAR consists of a single chain variable fragment (scFv) as the antigen recognition domain and CD3ζ as the T-cell signaling domain. Later generation CARs have at least one co-stimulating domain (e.g., CD27, CD28, CD134, CD137) and cytokine inducible domains (e.g., IL-12). Multi-targeting CARs have two or more sets of CARs on the surface of the T-cell.

Figure 4

Immune Checkpoint Molecule and Immune Checkpoint Inhibitor. (a) The combination of common immune checkpoint molecules and their ligands. (b) Simplified illustration of the immune checkpoint inhibitor mechanism. CTLA-4, Cytotoxic T-Lymphocyte Associated Protein 4; PD-1, Programed cell death 1; LAG-3, Lymphocyte Activating 3; TIM-3, T-cell immunoglobulin mucin-3; Gal-9, galectin-9; ICI, Immune checkpoint inhibitor; APC, antigen-presenting cell.

Figure 5

Comparison between osteosarcoma and ICI effective tumor cells. There are fewer immune cells and more suppressors cell in osteosarcoma, and there is less expression of major histocompatibility complex (MHC) and neoantigen on the surface of osteosarcoma.