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The m6A cluster 2 and high m6A score groups indicated a non-inflammatory phenotype, which may not be sensitive to immunotherapy but rather to targeted therapy. In this study, we first identified m6A clusters and m6A scores to elucidate immune phenotypes and to predict the prognosis and immunotherapy response in KIRC, which can guide urologists for making more precise clinical decisions.Background Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet. Methods A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included. Results At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enrichedpeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.Patient-derived cancer organoids have taken a prominent role in pre-clinical and translational research and have been generated for most common solid tumors. Cancer organoids have been shown to retain key genetic and phenotypic characteristics of their tissue of origin, tumor subtype and maintain intratumoral heterogeneity and therefore have the potential to be used as predictors for individualized treatment response. In this review, we highlight studies that have used cancer organoids to compare the efficacy of standard-of-care and targeted combination treatments with clinical patient response. Furthermore, we review studies using cancer organoids to identify new anti-cancer treatments using drug screening. find more Finally, we discuss the current limitations and improvements needed to understand the full potential of cancer organoids as avatars for clinical management of cancer therapy.
Bladder urothelial carcinoma (BLCA) is one of the most common urinary system malignancies with a high metastasis rate. Cancer stem cells (CSCs) play an important role in the occurrence and progression of BLCA, however, its roles in bone metastasis and the prognostic stemness biomarkers have not been identified in BLCA.
In order to identify the roles of CSC in the tumorigenesis, bone metastasis and prognosis of BLCA, the RNA sequencing data of patients with BLCA were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) and the differential expressed genes (DEGs) were evaluated and identified. The associations between mRNAsi and the tumorigenesis, bone metastasis, clinical stage and overall survival (OS) were also established. The key prognostic stemness-related genes (PSRGs) were screened by Lasso regression, and based on them, the predict model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteror patients with BLCA based on 20 PSRGs. Besides, we also identified the regulatory network between key PSRGs and cancer gene sets in mediating the BLCA bone metastasis.
Immuno-oncology (IO) agents have demonstrated efficacy across many tumor types and have led to change in standard of care. In breast cancer, atezolizumab and pembrolizumab were recently FDA-approved in combination with chemotherapy specifically for patients with PD-L1-positive metastatic triple-negative breast cancer (TNBC). However, the single agent PD-1/PD-L1 inhibitors demonstrate only modest single agent efficacy in breast cancer. The purpose of this study was to investigate the efficacy of novel IO agents in patients with metastatic breast cancer (MBC), beyond TNBC, treated in phase I clinical trials at the University of Colorado.
We performed a retrospective analysis using a database of patients with MBC who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Hospital from January 1, 2012 to July 1, 2018. Patient demographics, treatments and clinical outcomes were obtained.
We identified 43 patients treated with an IO agent either as a single agent or in c in phase I clinical trials with an IO agent derived prolonged clinical benefit. Predictors of response to immunotherapy in breast cancer remain uncharacterized and further research is needed to identify these factors.
Our phase I experience demonstrates benefit from IO therapy that was not limited to patients with TNBC and confirms improved efficacy from IO agents in combination with chemotherapy. A subset of patients with MBC treated in phase I clinical trials with an IO agent derived prolonged clinical benefit. Predictors of response to immunotherapy in breast cancer remain uncharacterized and further research is needed to identify these factors.
Although Polymerase-epsilon (POLE)-mutated and mismatch repair (MMR)-deficient endometrial cancers (ECs) are considered as promising candidates for anti-PD-1/PD-L1 therapy, selecting only these patients may exclude other patients who could potentially respond to this treatment strategy, highlighting the need of additional biomarkers for better patient selection. This study aims to evaluate potential predictive biomarkers for anti-PD-1/PD-L1 therapy in addition to POLE mutation (POLEm) and MMR deficiency (MMRd).
We performed next generation sequencing for POLE from 202 ECs, and immunohistochemistry for MLH1, MSH2, MSH6, PMS2, CD3, CD8, PD-1 and PD-L1 on full-section slides from these ECs. We assessed the association of POLEm and MMRd with clinicopathologic features, expression of check point proteins, and density of tumor-infiltrating lymphocytes (TILs). Prognostic impact of these immune markers was also evaluated.
POLEm, MMRd and high-grade tumors exhibited elevated level of TILs. Increased expression of PD-1 and PD-L1 was observed in MMRd and high-grade ECs.
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