The requirement for immune infiltration and organization in the tumor microenvironment for successful immunotherapy in prostate cancer

Abstract

Immunotherapy-particularly immune checkpoint blockade-has seen great success in many tumor types. However, checkpoint-based therapies have not demonstrated high levels of success in prostate cancer, and there is much to be learned from both the successes and failures of these treatments. Here we review the evidence that composition of infiltrating immune cells in the tumor microenvironment is fundamental to the response to immunotherapy. Additionally, we discuss the emerging idea that the organization of these immune cells may also be crucial to this response. In prostate cancer, the composition and organization of the tumor immune microenvironment are preeminent topics of discussion and areas of important future investigation.

Keywords: T-cell; cancer; checkpoint blockade; dendritic cell; immune; immunotherapy; macrophage; microenvironment; prostate; stroma; tertiary lymphoid structure; therapeutic vaccination.

Figure 1.

The tumor immune microenvironment can support or thwart the anti-tumor immune response. Infiltrating lymphocytes can kill tumor cells via cytotoxic granules containing granzymes and perforin. Dendritic cells and lymphocytes can organize, with the support of lymphoid-like stromal cells, to form tertiary lymphoid structures—dynamic aggregates that fuel the anti-tumor immune response. Alternatively, a dense, immunosuppressive stroma can limit T-cell activity, and pro-tumorigenic macrophages can support tumor growth and suppress cytotoxic T-cell activity.