Immunotherapy for Prostate Cancer

Abstract

Immunotherapy with agents that block immune checkpoints is a mainstay of therapy for several common tumor types; so far, prostate cancer is not among those treated using this method. The observed lack of activity in prostate cancer is not due to a lack of testing; several agents have been evaluated both alone and in combination. Although several combination strategies show some promise, it appears likely that a greater understanding of the prostate cancer tumor microenvironment and baseline immune response will be required to optimize future treatment strategies.

Figure 1.

Adaptive immune resistance and reinvigoration of antitumor immunity by programmed death-1 (PD-1) blockade. (A–H) PD-1 is up-regulated by antigen recognition, leading to secretion of the effector cytokine interferon (IFN)-γ. Sensing of IFN-γ by tumor cells results in up-regulation of PD-L1, which binds to PD-1 on the effector T cell, strongly inhibiting T-cell effector function and adaptive immunity. PD-1 blockade inhibits this negative interaction, leading to reacquisition of T-cell effector function and tumor lysis.

Figure 2.

Ligand for programmed death-1 (PD-L1) expression in metastatic prostate cancer. (A,B) Immunohistochemistry for PD-L1 in metastatic prostate cancer lesions. The majority of stained lesions are completely PD-L1-negative (A); ∼30% stain positive for PD-L1. (Images courtesy of M. Haffner, Johns Hopkins University.)

Figure 3.

Direct and cross-presentation of vaccine-encoded antigens. (A) Direct presentation. The vector directly infects antigen-presenting cell, leading to processing and presentation of tumor antigen on class I major histocompatibility complex (MHC). (B) Cross-presentation. The vector infects epithelial cells, leading to lysis. Cellular debris is taken up by nearby antigen presenting cells, processed, and presented on class I MHC.