The cancer journal
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Immune checkpoint therapy has started a revolution in the field of oncology. The concept that the immune system plays a critical role in antitumor responses, which has been around for decades, has finally been proven and firmly established with elegant preclinical studies and dramatic clinical responses in patients as a result of antibodies that block inhibitory T-cell pathways. However, the clinical responses being achieved are only in a subset of patients, and more work is needed to provide a better understanding of the mechanisms that elicit tumor rejection, which will enable identification of appropriate biomarkers, reveal new targets, provide data to guide combination studies, and eventually dictate a platform that allows more patients to derive clinical benefit, including cures, with immune checkpoint therapy.
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Immune checkpoint inhibition will be the first treatment breakthrough in recurrent and metastatic urothelial carcinoma since the introduction of combination chemotherapy more than 30 years ago. Monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4, programmed death receptor 1, and programmed death receptor ligand 1 are furthest along in clinical development. Specific antibodies targeting either programmed death receptor 1 or programmed death receptor ligand 1 have demonstrated significant single-agent activity with impressive safety and tolerability for heavily pretreated patients in early-phase clinical trials. In our review, we discuss the rationale for immunotherapy in urothelial cancer, completed and ongoing studies with immune checkpoint therapy, the development of molecular subtypes of urothelial carcinoma with the potential impact of immunotherapy in these new groupings, and future directions of exploration with these agents in both early- and late-stage disease.
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Most patients with head and neck squamous cell cancer (HNSCC) will present with advanced disease characterized by poor prognosis and limited treatment options. Our growing understanding of the complex crosstalk between tumor cells and the immune system has facilitated the development of promising therapies targeting immune checkpoints, such as programmed death 1 and the cytotoxic T-lymphocyte antigen 4, which are producing considerable clinical responses. ⋯ This may be counteracted by optimizing the dosing, sequence, and timing of immune checkpoint therapies and by combining these regimens with other modalities such as radiation therapy, cancer vaccines, cytotoxic chemotherapies, and molecularly targeted agents. The present review summarizes the pathophysiological role of immune regulation in HNSCC and provides a concise update on the clinical translation of immune checkpoint therapies in this tumor type.