Gorelov Ai

We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.

Treatment of bladder cancer has evolved over time to include the traditional modalities of chemotherapy and surgery, and it has been greatly impacted by the use of immunotherapy. Modern immunotherapy focuses on checkpoint protein inhibitors, which are molecules impeding immune function, thereby allowing unregulated tumor cell growth and proliferation. Several immune checkpoint targets (programmed death ligand-1 [PD-L1], programmed cell death protein-1 [PD-1], and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]) have received the most attention in the treatment of bladder cancer, whereas inhibitor agents have either been approved or are in late-stage development. This review describes the most recent data on PD-L1-inhibiting agents, found on the surface of tumor cells, and PD-1, found on activated T and B cells and macrophages. Aim. A review of modern PD-1 and PD-L1 inhibitors as target immunotherapeutic agents for the treatment of bladder cancer. Materials and methods. We performed a comprehensive literature review using MEDLINE/PubMed and EMBASE. Results. The PD-1/PD-L1 pathway is possibly manipulated by cancer cells to suppress the immune system. PD-1/PD-L1 blockade has been tested in clinical trials for various malignancies, including metastatic urothelial carcinoma, with significant response rates and limited adverse effects. PD-L1 expression has mixed results as a prognostic marker for bladder cancer. Conclusions. PD-1 is a key receptor mediating immune escape, and agents targeting its ligand, PD-L1, have already been successful in patients with metastatic urothelial cancer. Further research is warranted to standardize the criteria for PD-L1 positivity and to optimize its use in the treatment of bladder cancer. (For citation: Gorelov AI, Simbirtsev AS, Zhuravskiy DA, Gorelova AA. A review of the PD-1/PD-l1 checkpoint in bladder cancer: from mediator of immune escape to target for treatment. Urologicheskie vedomosti. 2018;8(2):64-72. doi: 10.17816/uroved8264-72).

3009 Background: Vitespen (formerly HSPPC-96) is a novel, autologous, heat shock protein (gp96)-peptide complex vaccine. The survival registry is investigating long-term efficacy of vitespen in renal cell carcinoma (RCC) patients at high risk for recurrence postnephrectomy. Methods: Eligible patients were enrolled and active in Antigenics’ C-100–12 phase III protocol, with a last survival status of alive at study end. Patients randomized in C-100–12 (1:1, vitespen vs. observation) had AJCC stage I (T1b), II (≥5 cm; Fuhrman grade 3/4), stage III, or stage IV (M0) RCC, ≥25% clear cells, ECOG performance score 0/1 and ≥7 g viable tumor tissue for vaccine production. The registry's primary objective is to assess OS. Registry patients are contacted every 6 (no recurrence) or 3 (upon recurrence) m, for a total of 3 y from final C-100–12 data cutoff. Results: Upon C-100–12 termination, 513 of 728 patients were eligible for follow-up. Currently, 306/513 (60%) patients are in the registry database; 207 patients are being contacted. The cohort of 306 patients is well balanced by C-100–12 randomization arm: (59.8% vitespen, 59.5% observation). Formal statistical analyses are in process. Descriptively, updated OS data show a favorable trend in the vitespen arm vs. observation in all analysis sets, especially among patients with earlier-stage disease (stage I/II high grade; n = 118) or at intermediate risk for recurrence (stage I/II high grade, III T1, T2, T3a, low grade; n = 184 ), with 13/125 (10.4%) vs. 21/115 (18.3%), and 18/184 (9.8%) vs. 33/178 (18.5%) deaths reported in the vitespen and observation arms, respectively. Conclusions: The registry provides an opportunity to confirm whether the emerging survival advantage demonstrated at the data cutoff for the C-100–12 trial improves with prolonged follow-up. Formal statistical analyses are ongoing; data available to date show continuing signals of clinical benefit associated with vitespen treatment in patients with better prognostic factors. [Table: see text]