The Changing Landscape of Immunotherapy for Advanced Renal Cancer

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Renal-cell carcinoma.

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Nonmyeloablative allogeneic peripheral blood stem-cell transplantation as immunotherapy for malignant diseases.

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A new member of the immunoglobulin superfamily--CTLA-4.

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CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.

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Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.

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Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade.

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T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.

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CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.

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Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.

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PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells.

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Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.

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Immune-related adverse events with immune checkpoint blockade: a comprehensive review.

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Nivolumab versus everolimus in patients with advanced renal cell carcinoma: updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial.

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Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.

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Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma.

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Von Hippel-Lindau disease.

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Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents.

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Identification of the von Hippel-Lindau disease tumor suppressor gene.

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Comprehensive molecular characterization of clear cell renal cell carcinoma.

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Pseudohypoxic pathways in renal cell carcinoma.

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The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer.

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Targeting the HIF2-VEGF axis in renal cell carcinoma.

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mTOR signaling in growth, metabolism, and disease.

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Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2.

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The great escape; the hallmarks of resistance to antiangiogenic therapy.

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Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats.

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Decreased antigen presentation by dendritic cells in patients with breast cancer.

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Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo.

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Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics.

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Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells.

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Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma.

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Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy.

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Axitinib augments antitumor activity in renal cell carcinoma via STAT3-dependent reversal of myeloid-derived suppressor cell accumulation.

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Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.

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Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

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Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma.

N Engl J Med. 384: 1289-1300Choueiri T.K. Powles T. Burotto M. et al.

Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma.

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Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial.

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Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial.

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Final overall survival and molecular analysis in IMmotion151, a phase 3 trial comparing atezolizumab plus bevacizumab vs sunitinib in patients with previously untreated metastatic renal cell carcinoma.

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N Engl J Med. 377: 2500-2501Latham A. Srinivasan P. Kemel Y. et al.

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Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma. J Immunother Cancer.

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Programmed cell death ligand 1 and tumor-infiltrating lymphocyte status in patients with renal cell carcinoma and sarcomatoid dedifferentiation.

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Progressive immune dysfunction with advancing disease stage in renal cell carcinoma.

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Cancer Discov. 9: 510-525Davidsson S. Fiorentino M. Giunchi F. et al.

Infiltration of M2 macrophages and regulatory T cells plays a role in recurrence of renal cell carcinoma.

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High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade.

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IL-8 and cancer prognosis on immunotherapy.

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LAG-3 as a potent target for novel anticancer therapies of a wide range of tumors.

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CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

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A phase I trial of vaccination of CA9-derived peptides for HLA-A24-positive patients with cytokine-refractory metastatic renal cell carcinoma.

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