Combining radiotherapy with immunocheckpoint inhibitors or CAR-T in Renal Cell Carcinoma.

Combining radiotherapy with immunocheckpoint inhibitors or CAR-T in Renal Cell Carcinoma. Curr Drug Targets. 2019 Oct 17;: Authors: Santoni M, Heng DY, Aurilio G, Iozzelli A, Servi L, Fabiani A, Giannini M, Mazzucchelli R, Cimadamore A, Scarpelli M, Zaghloul MS, Battelli N, Montironi R Abstract Radiotherapy is living a second life in Renal Cell Carcinoma (RCC) patients, mainly due to the introduction of immunocheckpoint inhibitors, such as anti-Programmed-death (PD)-1, alone or in combination with anti-Cytotoxic T-Lymphocyte Antigen (CTLA)-4. Several trials are investigating the efficacy/safety of immunocheckpoint inhibitors in sequential or combined strategies with radiotherapy. Chimeric Antigen Receptor (CAR)-T cells therapy as a promising approach in cancer patients has opened the way to novel possibilities of integrating therapies. The identification of biomarkers of tumor response to these combinations represents a challenge in RCC, together with the research for the best partner for immunotherapy in metastatic patients. In this review we illustrated preclinical/clinical data on the integration of radiotherapy with immunocheckpoint inhibitors or CAR-T cells in RCC. PMID: 31625471 [PubMed - as supplied by publisher]
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research

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ConclusionsMultiple cytokines found in an immune-reactive TME may induce PD-L1 expression on tumor and/or immune cells through distinct signaling mechanisms. Factors driving constitutive PD-L1 expression were not identified in this study. Understanding complex mechanisms underlying PD-L1 display in the TME may allow treatment approaches mitigating expression of this immunosuppressive ligand, to enhance the impact of PD-1 blockade.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionIn renal cell carcinoma, rapid and successful drug development has resulted in multiple treatment options, requiring careful decision making for individual patients and have emphasized how newly developed therapies work.
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
Abstract The combined immunotherapy of nivolumab and ipilimumab causes a variety of autoimmune-related adverse events (irAEs). The current report details a 70-year-old woman with clear cell renal cell carcinoma metastasis in the lung. Two weeks after two courses of treatment, the patient complained of headache, dizziness and nausea. Cerebrospinal fluid (CSF) analysis revealed an elevated protein level of 195 mg/dl and a significantly elevated white blood cell (WBC) count of 830/mm3 (lymphocytes, 825/mm3; neutrophils, 5/mm3). The results excluded malignancy and infection. The patient was diagnosed with aseptic meni...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Mol Clin Oncol Source Type: research
grave;res J Abstract Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible...
Source: Respiratory Care - Category: Respiratory Medicine Authors: Tags: Eur Respir Rev Source Type: research
CONCLUSIONS: To properly identify and predict response after treatment with ICI, additional studies with long-term follow-ups are needed. Because of the growing use of ICI, radiologists and urologist should be familiar with common imaging findings (such as pseudo progress) under immunotherapy to correctly interpret these findings in daily routine. PMID: 31705144 [PubMed - as supplied by publisher]
Source: Der Urologe. Ausg. A - Category: Urology & Nephrology Authors: Tags: Urologe A Source Type: research
Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Altho...
Source: European Respiratory Review - Category: Respiratory Medicine Authors: Tags: Pulmonary pharmacology and therapeutics Reviews Source Type: research
In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and β chain (TRB) genes. Full-lengthTRA andTRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven uniqueTRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-tran...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Introduction: The prognosis for recurrent intrahepatic cholangiocarcinoma with bone metastasis remains dismal and its treatment poses a challenge for oncologists. To date, only 2 cases were reported in which pembrolizumab, an agent against programmed cell death protein-1 (PD-1), combined with chemotherapy led to a complete response.[1] The safety and efficacy of nivolumab-based immunotherapy combined with lenvatinibin intrahepatic cholangiocarcinoma is unknown. Patient concerns: A 40-year-old female was identified as having a lesion of 7.0 cm in diameter in the right lobe of the liver. In addition, calculi in the ma...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
CONCLUSION: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy. METHODS: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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