TFEB mediates immune evasion and resistance to mTOR inhibition of renal cell carcinoma via induction of PD-L1.

CONCLUSIONS: These data revealed that TFEB mediates resistance to mTOR inhibition via induction of PD-L1 in human primary RCC tumors, RCC cells and murine xenograft model. Our data provide a strong rationale to target mTOR and PD-L1 jointly as a novel immunotherapeutic approach for RCC treatment. PMID: 31383732 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

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CONCLUSION: Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with>20% rhabdoid; further randomized clinical trials are warranted. IMPLICATIONS FOR PRACTICE: This article reports on the clinical activity and safety of immune checkpoint inhibitors in non-clear cell kidney cancer. The retrospective data with the meta-analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers. PMID: 31501271 [PubMed - as supplied by publisher]
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Authors: Gandhi JS, Malik F, Amin MB, Argani P, Bahrami A Abstract Microphthalmia (MiT) family translocation renal cell carcinomas (RCCs) are a heterogeneous category of renal tumors which all express MiT transcription factors, typically from chromosomal translocation and rarely from gene amplification. This tumor family has two major subtypes [i.e., Xp11 translocation RCC and t(6;11) RCC] and several related neoplasms (i.e., TFEB amplification RCC and melanotic Xp11 translocation renal cancers). Increased understanding of the clinical, pathological, molecular and prognostic heterogeneity of these tumors, since the...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
ido Martignoni The new category of MiT family translocation renal cell carcinoma has been included into the World Health Organization (WHO) classification in 2016. The MiT family translocation renal cell carcinoma comprises Xp11 translocation renal cell carcinoma harboring TFE3 gene fusions and t(6;11) renal cell carcinoma harboring TFEB gene fusion. At the beginning, they were recognized in childhood; nevertheless, it has been demonstrated that these neoplasms can occur in adults as well. In the nineties, among Xp11 renal cell carcinoma, ASPL, PRCC, and SFPQ (PSF) were the first genes recognized as partners in TFE3 re...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we examined the anti-tumor effect of the antibody toxin conjugate (ADC) against activated matriptase positive mantle cell lymphoma cell lines (JeKo-1, Maver, Mino, and Z138). This ADC was cytotoxic to these cell lines with IC50s between 5 and 14 μg/mL. The ADC also showed a dose dependent anti-tumor effect on the JeKo-1 xenograft in mice without toxicity. Introduction Mantle Cell Lymphoma (MCL), represents 6- percent of all lymphoma cases, and currently the survival time is 4–5 years, shorter compared to other hematologic malignancies (2–4). MCL cells express CD20, aberrant expression ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Translocation renal cell carcinomas (tRCC) encompass a diverse group of tumors affecting younger patients, and often progressing as metastases. Accurate diagnosis is required to guide clinical management. Morphologic and immunohistochemical findings can prompt reflex FISH studies, but with several significant limitations. A better molecular assay is needed.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
ConclusionProper differentiation of RCCs related to translocation of MiT family requires immunostaining for TFE3, especially in the case of younger patients, among which the prevalence of this genetic mutation is frequent.
Source: Journal of Pediatric Surgery Case Reports - Category: Surgery Source Type: research
Xp11.2 translocation renal cell carcinoma (tRCC) is mainly caused by translocation of the TFE3 gene located on chromosome Xp11.2 and is characterized by overexpression of the TFE3 fusion gene. Patients are dia...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
This study aims to evaluate the frequency of RCC with Xp11.2 in a subset of Saudi adult patients with RCC. 112 RCCs diagnosed in 1995-2016 were retrieved from the Department of Pathology at King Abdulaziz University and King and Faisal Specialist Hospital and Research Centre, Saudi Arabia. Tissue microarrays were constructed and TFE3 immunostaining was performed. TFE3 immunostaining was considered positive when diffuse strong nuclear immunostaining was detected. TFE3 immunostaining-positive tumours were confirmed by fluorescence in situ hybridisation. 4.5% of RCCs were shown to be Xp11.2 RCC by TFE3 immunostaining. TFE3-po...
Source: Polish Journal of Pathology - Category: Pathology Tags: Pol J Pathol Source Type: research
AbstractThe 2016 WHO Classification of Tumors of the Urinary System recognizes microphthalmia transcription factor (MiT) family translocation carcinomas as a separate entity among renal cell carcinomas. TFE3 and transcription factor EB (TFEB) are members of the MiT family for which chromosomal rearrangements have been associated with renal cell carcinoma formation. TFEB translocation renal cell carcinoma is a rare tumor harboring a t(6;11)(p21;q12) translocation. Recently, renal cell carcinomas with TFEB amplification have been identified. TFEB amplified renal cell carcinomas have to be distinguished from TFEB-translocated...
Source: Virchows Archiv - Category: Pathology Source Type: research
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