In this review, we summarized latest clinical development of PD antibodies and immunohistochemistry (IHC) assays for PD-L1 biomarker expression in clinical practice. New development in clinical applications of PD-1 and PD-L1 antibodies The US Food and Drug Administration (FDA) has approved 5 immune checkpoint blockers in 11 types of advanced malignancies (Table?1). Table 1 Clinical applications of PD-1 and PD-L1 antibodies non-small cell lung cancer, head/neck squamous cell carcinoma, microsatellite instability; deficient mismatch repair gene, colorectal cancer, hepatocellular carcinoma, minute, every 3?weeks aFfor pediatric dosing and for combination dosage and schedules, please refer to full prescribing information for each individual agent bFor exact indications, please refer to full prescribing information for each individual agent Nivolumab has FDA approved indications for treatment of eight types of advanced malignancies. trials. This review summarized recent development in clinical trials of PD-1 and PD-L1 antibodies for cancer immunotherapy. Background Targeted therapies for cancer with small molecules and monoclonal antibodies (MoAb) have led to significant improvement in the long-term survival of multiple malignancies [1C11]. The discovery of programmed death-1 (PD-1) and the ligand 1 (PD-L1) has opened the door to the Procainamide HCl modern era of cancer immunotherapy [12, 13]. It is well known now that many tumor cells are able to upregulate the expression of PD-L1 which leads to anergy of cytotoxic T cells upon PD-1 binding to the ligand. Blocking the PD-1 pathway using monoclonal antibodies against PD-1 or PD-L1 can therefore revamp the immune response against tumor cells [14]. The development of MoAbs against PD-1 and PD-L1 Procainamide HCl has led to the fast and fundamental paradigm shift in cancer therapy [15]. The anti-PD drugs are the new form of tumor-site immune modulation therapy through resetting immune reservoir in the tumor microenvironment [16, 17]. This is fundamentally different from the conventional chemotherapy and radiation that mainly target cancer cells themselves. PD-L1 expression around the tumor cells and immune cells have become biomarkers that can assist clinical decisions in the choice of treatment strategies [18, 19]. Biomarker assays for PD-L1 are playing bigger roles and are being routinely done nowadays. However, PD-L1 assays can be highly variable, which makes it a clinical challenge to employ the results. In this review, we summarized latest clinical development of PD antibodies and immunohistochemistry (IHC) assays for PD-L1 biomarker expression in clinical practice. New development in clinical applications of PD-1 and PD-L1 antibodies The US Food and Drug Administration (FDA) has approved 5 immune checkpoint blockers in 11 types Procainamide HCl of advanced malignancies (Table?1). Procainamide HCl Table 1 Clinical applications of PD-1 PRKAA2 and PD-L1 antibodies non-small cell lung cancer, head/neck squamous cell carcinoma, microsatellite instability; deficient mismatch repair gene, colorectal cancer, hepatocellular carcinoma, minute, every 3?weeks aFfor pediatric dosing and for combination dosage and schedules, please refer to full prescribing information for each individual agent bFor exact indications, please refer to full prescribing information for each individual agent Nivolumab has FDA approved indications for treatment of eight types of advanced malignancies. These malignancies include melanoma, NSCLC (non-small cell lung cancer), classical Hodgkin lymphoma, HNSCC (squamous cell carcinoma of the head and neck), renal cell carcinoma, urothelial carcinoma, hepatocellular carcinoma, and microsatellite instability (MSI)-high or mismatch repair gene (MMR)-deficient colorectal cancer (Table?1) [20C35]. It has been observed that pneumonitis may be associated with responses to PD antibodies [36, 37]. Nivolumab is being explored in more and more cancer types. Twenty patients with platinum-resistant ovarian cancer were treated with nivolumab in a phase II trial. Patients received up to six cycles (four doses per cycle). Twenty nivolumab-treated patients were evaluable at the time of the report and found to have ORR of 15%. Two of the responding patients had a durable CR (in the 3?mg/kg cohort). At the termination of the study, the median PFS was 3.5?months and the median overall survival (OS) was 20.0?months. The encouraging results from this pilot study of nivolumab in patients with platinum-resistant ovarian cancer suggest potential benefit of PD-1 antibody for refractory ovarian cancer [38]. Nivolumab is being studied in a phase I trial as a maintenance therapy for patients with high-risk hematological malignancies (“type”:”clinical-trial”,”attrs”:”text”:”NCT02985554″,”term_id”:”NCT02985554″NCT02985554). Procainamide HCl More than 350 trials of nivolumab have been registered on clinicaltrials.gov. Currently, pembrolizumab has FDA approved indications of seven different types of advanced malignancies. These malignancies include melanoma [39, 40], NSCLC [41C44], HNSCC, urothelial carcinoma, Hodgkins lymphoma [45], and gastric cancer [46, 47] (Table?1). Among these, FDA approved one indication for any malignancy with high microsatellite instability or mismatch repair gene (MMR) deficiency [48]. However, response to pembrolizumab in a gastric patient with stable MSI and proficient MMR has been observed [49]. Pembrolizumab has also been reported to be active in other highly refractory malignancies, such as Ewings sarcoma [50]. Recently, pembrolizumab was reported to be active in patients with refractory large cell lymphoma of the mediastinum [51]. Pembrolizumab has been studied in 26 patients with advanced Merkel cell carcinoma who had not received previous systemic.