Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease

alexandrossfakianakis shared this article with you from Inoreader Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease via Clinical Infectious Diseases Advance Access Abstract The emergence of new SARS-COV-2 variants is of public health concern in case of vaccine escape. Described are three patients with advanced HIV-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations which are associated with increased transmissibility and immune escape. View on Web

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CSMD1 suppresses cancer progression by inhibiting proliferation, epithelial-mesenchymal transition, chemotherapy-resistance and inducing immunosuppression in esophageal squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader CSMD1 suppresses cancer progression by inhibiting proliferation, epithelial-mesenchymal transition, chemotherapy-resistance and inducing immunosuppression in esophageal squamous cell carcinoma via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 25 May 2022 Source: Experimental Cell Research Author(s): Xing Wang, Xinwei Chen, Yuanyuan Liu, Shan Huang, Jian Ding, Baoxin Wang, Pin Dong, Zhenfeng Sun, Lixiao Chen View on Web

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Association of breakfast consumption frequency with fasting glucose and insulin sensitivity/b cells function (HOMA-IR) in adults from high-risk families for type 2 diabetes in Europe: the Feel4Diabetes Study

alexandrossfakianakis shared this article with you from Inoreader Association of breakfast consumption frequency with fasting glucose and insulin sensitivity/b cells function (HOMA-IR) in adults from high-risk families for type 2 diabetes in Europe: the Feel4Diabetes Study via European Journal of Clinical Nutrition - Issue - nature.com science feeds European Journal of Clinical Nutrition, Published online: 25 May 2022; doi:10.1038/s41430-022-01160-z Association of breakfast consumption frequency with fasting glucose and insulin sensitivity/b cells function (HOMA-IR) in adults from high-risk families for type 2 diabetes in Europe: the Feel4Diabetes Study View on Web

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Serum uric acid is not associated with major depressive disorder

alexandrossfakianakis shared this article with you from Inoreader Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study via European Journal of Clinical Nutrition - Issue - nature.com science feeds European Journal of Clinical Nutrition, Published online: 25 May 2022; doi:10.1038/s41430-022-01165-8 Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study View on Web

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Dysfunctional dendritic cells limit antigen-specific T cell response in glioma

alexandrossfakianakis shared this article with you from Inoreader Dysfunctional dendritic cells limit antigen-specific T cell response in glioma via Neuro-Oncology Advance Access Abstract Background Dendritic cells (DC), the most potent professional antigen presenting cells capable of effective cross-presentation, have been demonstrated to license T helper cells to induce anti-tumor immunity in solid tumors. Specific DC subtypes are recruited to the injured brain by microglial chemokines, locally adapting to distinct transcriptional profiles. In isocitrate dehydrogenase type 1 (IDH) mutant gliomas, monocyte-derived macrophages have recently been shown to display an attenuated intratumoral antigen presentation capacity as consequence of the local accumulation of the oncometabolite R-2-hydroxyglutarate. The functionality and the contribution of DC to the IDH-mutant tumor microenvironment (TME) remains unclear. Methods Frequencies and intratumoral phenotypes of human DC in IDH-wildtype and -mutant high-grade gliomas are comparatively assessed by transcriptomic and proteomic profiling. DC functionality is investigat ed in experimental murine glioblastomas expressing the model antigen ovalbumin. Single-cell sequencing-based pseudotime analyses and spectral flow cytometric analyses are used to profile DC states longitudinally. Results DC are present in primary and recurrent high-grade gliomas and interact with other immune cell types within the TME. In murine glioblastomas, we find an IDH-status-associated major histocompatibility class I-restricted cross-presentation of tumor antigens by DC specifically in the tumor but not in meninges or secondary lymphoid organs of tumor-bearing animals. In single-cell sequencing-based pseudotime and longitudinal spectral flow cytometric analyses, we demonstrate an IDH-status-dependent differential, exclusively microenvironmental education of DC. Conclusion Glioma-associated DCs are relevantly abundant in human IDH wildtype and mutant tumors. Glioma IDH mutations result in specifically educated, dysfunctional DCs via paracrine reprogramming o f infiltrating monocytes, providing the basis for combinatorial immunotherapy concepts against IDH mutant gliomas. View on Web

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A comprehensive profiling of the immune microenvironment of breast cancer brain metastases

alexandrossfakianakis shared this article with you from Inoreader A comprehensive profiling of the immune microenvironment of breast cancer brain metastases via Neuro-Oncology Advance Access Abstract Background Despite potential clinical implications, the complexity of breast cancer (BC) brain metastases (BM) immune microenvironment is poorly understood. Through multiplex immunofluorescence, we here describe the main features of BCBM immune microenvironment (density and spatial distribution) and evaluate its prognostic impact. Methods 60 BCBM from patients undergoing neurosurgery at three institutions (2003-2018) was comprehensively assessed using two multiplex immunofluorescence panels (CD4, CD8, Granzyme B, FoxP3, CD68, pan-cytokeratin, DAPI; CD3, PD-1, PD-L1, LAG-3, TIM-3, CD163, pan-cytokeratin, DAPI). The prognostic impact of immune subpopulations and cell-to-cell spatial interactions was evaluated. Results Subtype-related differences in BCBM immune microenvironment and its prognostic impact were observed. While in HR-/HER2- BM and HER2+ BM, higher densities of intra-tumoral CD8+ lymphocytes were associated wi th significantly longer OS (HR 0.16 and 0.20, respectively), in HR+/HER2- BCBMs a higher CD4+FoxP3+/CD8+ cell ratio in the stroma was associated with worse OS (HR 5.4). Moreover, a higher density of intra-tumoral CD163+ M2-polarized microglia/macrophages in BCBMs was significantly associated with worse OS in HR-/HER2- and HR+/HER2- BCBMs (HR 6.56 and 4.68, respectively), but not in HER2+ BCBMs. In HER2+ BCBMs, multiplex immunofluorescence highlighted a negative prognostic role of PD-1/PD-L1 interaction: patients with a higher percentage of PD-L1+ cells spatially interacting with (within a 20 µm radius) PD-1+ cells presented a significantly worse OS (HR 4.60). Conclusions Our results highlight subtype-related differences in BCBM immune microenvironment and identify two potential therapeutic targets, M2 microglia/macrophage polarization in HER2- and PD-1/PD-L1 interaction in HER2+ BCBMs, which warrant future exploration in clinical trials. View on Web

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Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: a multicenter, open-label, phase 1b/2 trial

alexandrossfakianakis shared this article with you from Inoreader Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: a multicenter, open-label, phase 1b/2 trial via Neuro-Oncology Advance Access Abstract Background Olutasidenib (FT2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1  R132X mutation. Methods This was an open-label, multicenter, non-randomized, phase 1b/2 clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1  R132Xmutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase 1 and objective response rate using the Modified Res ponse Assessment in Neuro-Oncology criteria in phase 2. Results Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase 2 dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Conclusions Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1  R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated populat ion. View on Web

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