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Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in solid tumors


Immune checkpoint inhibitors have been identified as breakthrough treatment in melanoma given its dramatic response to PD-1/PD-L1 blockade. This is likely to extend to many other cancers as hundreds of clinical trials are being conducted or proposed using this exciting modality of therapy in a variety of malignancies. While immune checkpoint inhibitors have been extensively studied in melanoma and more recently in lung cancer, little is known regarding immune checkpoint blockade in other cancers. This review will focus on the tumor immune microenvironment, the expression of PD-1/PD-L1 and the effect of immune modulation using PD-1 or PD-L1 inhibitors in patients with head and neck, prostate, urothelial, renal, breast, gastrointestinal and lung cancers.

The discovery of immune checkpoints represents a new era in cancer treatment. Recently, it became evident that tumors can hijack the immune tolerance mechanism by overexpressing these immune checkpoints placing a brake on the activation of immune system [1]. Inhibiting these immune checkpoints or their ligands can lift the break on the immune system leading to a powerful immune response against tumor cells. Not surprisingly, immune checkpoints were first investigated in melanoma given the well-known immunogenic nature of this malignancy [2]. The CTLA-4 antibody ipilimumab was the first immune checkpoint inhibitor that showed activity in melanoma treatment [2] followed by PD-1 inhibitors [3,4]. Since then many studies have been conducted to expand the indication of immune checkpoints beyond melanoma. This review will focus on these studies targeting PD-1/PD-L1 pathway in cancers other than melanoma.

Click here to view the full article in Immunotherapy.