IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.

Lymphatic vessels play a crucial role in activating anti-tumor immune surveillance but also contribute to metastasis and systemic tumor progression. Whether distinct lymphatic phenotypes exist that govern the switch between immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential.

Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment.

Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience.

Introduction: Compared with traditional static ice storage, controlled hypothermic storage (CHS) at 4-10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device.

Methods: A prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers.

Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction.

Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats.

Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration.

Biportal robotic pulmonary lobectomy, initial experience - case report.

Introduction: Thanks to perfect visualization and high maneuverability of instruments, the robotic technique is a preferable type of lung resection, even though the number of required incisions is usually higher compared to the video-assisted approach. This case report presents our initial experience with the reduced-port approach in performing robotic biportal lobectomy.

Case Report: The 72-years-old female, examined for hemoptysis, was diagnosed with a carcinoid tumor of the left lower lobe bronchus based on bronchoscopy.

Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma.

Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T-cells, thereby restricting melanoma growth.

Robotic pulmonary segmentectomy, initial experience in the Czech Republic.

Introduction: The initiation of lung cancer screening in Czechia and diagnosis in earlier stages has been reflected by an increasing demand for anatomical lung segmentectomy. The purpose of this study was to describe early results of the first robotic-assisted thoracoscopic segmentectomies performed in the country.

Methods: Our institution has performed 151 robotic anatomical lung resections since the initiation of the screening program in August 2020, which enabled us to attain the status of a proctoring and case observation centre.

Melanoma-intrinsic NR2F6 activity regulates antitumor immunity.

Nuclear receptors (NRs) are implicated in the regulation of tumors and immune cells. We identify a tumor-intrinsic function of the orphan NR, NR2F6, regulating antitumor immunity. NR2F6 was selected from 48 candidate NRs based on an expression pattern in melanoma patient specimens (i.

The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity.

The cell-autonomous balance of immune-inhibitory and -stimulatory signals is a critical process in cancer immune evasion. Using patient-derived co-cultures, humanized mouse models, and single-cell RNA-sequencing of patient melanomas biopsied before and on immune checkpoint blockade, we find that intact cancer cell-intrinsic expression of CD58 and ligation to CD2 is required for anti-tumor immunity and is predictive of treatment response. Defects in this axis promote immune evasion through diminished T cell activation, impaired intratumoral T cell infiltration and proliferation, and concurrently increased PD-L1 protein stabilization.

Glucocorticoid activation by HSD11B1 limits T cell-driven interferon signaling and response to PD-1 blockade in melanoma.

Background: Immune responses against tumors are subject to negative feedback regulation. Immune checkpoint inhibitors (ICIs) blocking Programmed cell death protein 1 (PD-1), a receptor expressed on T cells, or its ligand PD-L1 have significantly improved the treatment of cancer, in particular malignant melanoma. Nevertheless, responses and durability are variables, suggesting that additional critical negative feedback mechanisms exist and need to be targeted to improve therapeutic efficacy.

An adverse tumor-protective effect of IDO1 inhibition.

By restoring tryptophan, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors aim to reactivate anti-tumor T cells. However, a phase III trial assessing their clinical benefit failed, prompting us to revisit the role of IDO1 in tumor cells under T cell attack. We show here that IDO1 inhibition leads to an adverse protection of melanoma cells to T cell-derived interferon-gamma (IFNγ).

is commonly amplified and high expression in cancer cells correlates with poor immune checkpoint blockade response.

Immunotherapies, in particular immune checkpoint blockade (ICB), have improved the clinical outcome of cancer patients, although many fail to mount a durable response. Several resistance mechanisms have been identified, but our understanding of the requirements for a robust ICB response is incomplete. We have engineered an MHC I/antigen: TCR-matched panel of human NSCLC cancer and T cells to identify tumor cell-intrinsic T cell resistance mechanisms.

Application of Oil-in-Water Cannabidiol Emulsion for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them.

A cellular hierarchy in melanoma uncouples growth and metastasis.

Although melanoma is notorious for its high degree of heterogeneity and plasticity, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. Here, by combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest.

The first lung retransplantation with "ECMO bridge" in the Czech Republic - case report.

During the last 23 years of the National Lung Transplant Program in the Czech Republic, more than 500 lung transplantations, 4 retransplantations and one lobar retransplantation have been performed. We present the case report of a female patient with cystic fibrosis who underwent her first bilateral lung transplantation in January 2020. Due to a chronic lung allograft dysfunction, the patient required ECMO support and retransplantation.

Ex vivo lung evaluation of single donor lungs when the contralateral lung is rejected increases safe use.

Objective: The decision to perform a single-lung transplant (SLT) when the contralateral donor lung is rejected is a challenging scenario. The introduction of ex vivo lung perfusion (EVLP) has improved donor lung assessment, and we hypothesize that it has improved SLT outcomes in this setting.

Methods: A retrospective single-center review of all SLTs performed between 2000 and 2017 was performed in which the years 2000 to 2008 were considered the "pre-EVLP era" and 2009 to 2017 the "EVLP era.

Ganciclovir Pharmacokinetics and Individualized Dosing Based on Covariate in Lung Transplant Recipients.

The aim of this prospective study was to evaluate the pharmacokinetics of ganciclovir in lung transplant recipients, to explore its covariates, and to propose an individualized dosing regimen. Ganciclovir was administered according to the protocol in a standardized intravenous dose of 5 mg/kg twice daily. Serum ganciclovir concentrations were monitored as a trough and at 3 and 5 h after dosing.

Video-assisted and robotic-assisted thoracoscopic pulmonary lobectomies, our experience.

Introduction: The use of video-assisted (VATS) and robotic-assisted (RATS) thoracoscopic surgery for anatomical pulmonary resections has been rapidly increasing. This study aimed to analyze our results of minimal invasive lobectomies to safely introduce these techniques to our practice.

Methods: Starting these new programs we followed the recommended steps including case observations and a proctoring.

Starting the first robotic lobectomy program in the Eastern Europe during Coronavirus disease-2019 pandemic.

Background: We report our experience in starting RATS (robotic-assisted thoracic surgery) lobectomy program during COVID-19 pandemic.

Methods: Data from 20 consecutive cases undergoing RATS lobectomy between August 2020 and April 2021 were prospectively accumulated into our database.

Results: The mean operational time was 235±69 minutes (median 210, range 175 to 370).