Frontiers in oncology
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Frontiers in oncology · Jan 2020
Association of MSH2 Expression With Tumor Mutational Burden and the Immune Microenvironment in Lung Adenocarcinoma.
Immune checkpoint blockade (ICB) therapies that target programmed cell death 1 (PD1) and PD1 ligand 1 (PDL1) have demonstrated promising benefits in lung adenocarcinoma (LUAD), and tumor mutational burden (TMB) is the most robust biomarker associated with the efficacy of PD-1-PD-L1 axis blockade in LUAD, but the assessment of TMB by whole-exome sequencing (WES) is rather expensive and time-consuming. Although targeted panel sequencing has been developed and approved by the US Food and Drug Administration (FDA) to estimate TMB, we found that its predictive accuracy for ICB response was significantly lower than WES in LUAD. Given that previous studies were mainly focusing on genomic variations to explore surrogate biomarkers of TMB, we turned to examine the transcriptome-based correlation with TMB in this study. ⋯ Notably, detecting MSH2 expression is much easier, faster, and cheaper than TMB in clinical practice. Taken together, this study demonstrates the association of MSH2 expression with TMB and the immune microenvironment in LUAD. MSH2 expression may be developed as a potential surrogate biomarker of TMB to identify ICB responders in LUAD.
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Frontiers in oncology · Jan 2020
Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis.
The prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression. ⋯ Our findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.
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Frontiers in oncology · Jan 2019
Differentiation of Small Hepatocellular Carcinoma From Dysplastic Nodules in Cirrhotic Liver: Texture Analysis Based on MRI Improved Performance in Comparison Over Gadoxetic Acid-Enhanced MR and Diffusion-Weighted Imaging.
Background: Accurate characterization of small (3 cm) hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in cirrhotic liver is challenging. We aimed to investigate whether texture analysis (TA) based on T2-weighted images (T2WI) is superior to qualitative diagnosis using gadoxetic acid-enhanced MR imaging (Gd-EOB-MRI) and diffusion-weighted imaging (DWI) for distinguishing sHCC from DNs in cirrhosis. Materials and methods: Sixty-eight patients with 73 liver nodules (46 HCCs, 27 DNs) pathologically confirmed by operation were included. ⋯ The specificity of TA (92.6%) was significantly higher than that of the combined set (P < 0.001), but no significant difference was observed in sensitivity (97.8 vs. 95.6%, P = 0.559). Conclusion: TA-based T2WI showed a better classification performance than that of qualitative diagnosis using Gd-EOB-MRI and DW imaging in differentiation of sHCCs from DNs in cirrhotic liver. TA-based MRI may become a potential imaging biomarker for the early differentiation HCCs from DNs in cirrhosis.
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Cutaneous T cell lymphomas (CTCL) are a heterogeneous group of malignancies characterized by the expansion of a malignant T cell clone. Chimeric Antigen Receptor (CAR) T cell therapy has shown impressive results for the treatment of B-cell tumors, but several challenges have prevented this approach in the context of T cell lymphoma. These challenges include the possibilities of fratricide due to shared T-cell antigens, T cell immunodeficiency, and CAR transduction of malignant cells if CAR T are manufactured in the autologous setting. In this review, we discuss these and other challenges in detail and summarize the approaches currently in development to overcome these challenges and offer cellular targeting of T cell lymphomas.
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Frontiers in oncology · Jan 2019
Case ReportsVitiligo Adverse Event Observed in a Patient With Durable Complete Response After Nivolumab for Metastatic Renal Cell Carcinoma.
Background: Renal cell carcinoma is the third most prevalent urological cancer worldwide and about 30% of patients present with metastatic disease at the time of diagnosis. Systemic treatments for metastatic renal cell carcinoma have improved recently. Vascular endothelial growth factor targeting therapies were the previous standard of care. ⋯ Conclusions: Pathological complete response with nivolumab in metastatic renal cell carcinoma is rare. This case further highlights the potentially predictive role of immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma and raises questions concerning the role of nephrectomy after immune checkpoint inhibitor therapy. Further studies are needed to better identify predictive factors for treatment response to immunotherapy in metastatic renal cell carcinoma, and to better understand the role of nephrectomy after nivolumab treatment.