Prognostic immunoinflammatory and transcriptomic profiles in patients with pleural mesothelioma undergoing immunotherapy.

Aim: A translational multiscale approach, encompassing tumor immune microenvironment (TIME), circulating immune-inflammatory benchmarks, and transcriptomic profiles, was undertaken to identify prognostic biomarkers of immunotherapy (IT) efficacy in patients with advanced pleural mesothelioma (PM).

Methods: Advanced PM patients ( = 17) treated with nivolumab plus ipilimumab were prospectively enrolled in the FIL-QI 2021 study. Baseline blood and tumor samples were analyzed for immune subsets and functional markers (Granzyme B, Ki67) by flow cytometry, cytokines by multiplex ELISA, TILs and PD-L1 by immunohistochemistry, and gene expression by nanostring.

Role of Hb to RDW ratio in metastatic renal cell carcinoma patients treated with first-line immunotherapy combinations.

Background: The present study aimed to investigate the prognostic and predictive roles of Hb/RDW ratio in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).

Materials And Methods: We performed a sub-analysis of a multicenter retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations.

Results: Three hundred and twenty-nine patients were enrolled, 244 males and 85 females.

Longitudinal Blood Immune-Inflammatory and Radiomic Profiling to Decode Different Patterns of Acquired Resistance to Immunotherapy in Patients with NSCLC.

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinicopathologic, radiomic, and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in patients with advanced non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor therapy.

Experimental Design: On 105 consecutive patients with IO-treated advanced NSCLC, PB immunophenotypes, cytokines, and CT-derived radiomic features (RF), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and at the first disease assessment (T1, 9-12 weeks), and their Δ variation [(T1-T0)/T0] was computed. AR, defined as progression after the initial response (complete/partial) or stable disease ≥6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3).

CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase.

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered.

Differential impact of lipid profile according to neutrophil-to-lymphocyte ratio status in patients with advanced cancer treated with immunotherapy.

To investigate the different impact of each component of lipid profile in advanced cancer patients treated with immune checkpoints inhibitors (ICIs) according to neutrophil-to-lymphocyte ratio (NLR) value. We retrospectively collected total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL). 407 patients were enrolled.

Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors.

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α.

External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations.

Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI).

Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score.

Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs.

Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential.

Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC).

Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases.

The role of blood cholesterol quality in patients with advanced cancer receiving immune checkpoint inhibitors.

Introduction: Immune checkpoint inhibitors (ICIs) became the standard of care for several solid tumors. A limited fraction of patients (pts) achieves a long-term benefit. Plasmatic and intracellular cholesterol levels have emerged as promising biomarkers.

Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review.

Introduction: In spite of the undisputed relevance of sex as critical biologic variable of the immune landscape, still limited is our understanding of the basic mechanisms implicated in sex-biased immune response thereby conditioning the therapeutic outcome in cancer patients. This hindrance delays the actual attempts to decipher the heterogeneity of cancer and its immune surveillance, further digressing the achievement of predictive biomarkers in the current immunotherapy-driven scenario. : The present review concisely reports on genetic, chromosomal, hormonal, and immune features underlying sex-differences in the response to immune checkpoint inhibitors (ICIs).

Β-blockers activate autophagy on infantile hemangioma-derived endothelial cells in vitro.

Unlabelled: The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro.

Material And Methods: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion.

Integrated MRI-Immune-Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma.

Background: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features.

Methods: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant).

Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy.

The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance.

PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors.

Objective: To investigate the role of (programmed death-1), and (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).

Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups.

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development.

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients.

Validation of a radiomic approach to decipher NSCLC immune microenvironment in surgically resected patients.

Radiomics has emerged as a noninvasive tool endowed with the potential to intercept tumor characteristics thereby predicting clinical outcome. In a recent study on resected non-small cell lung cancer (NSCLC), we identified highly prognostic computed tomography (CT) -derived radiomic features (RFs), which in turn were able to discriminate hot from cold tumor immune microenvironment (TIME). We aimed at validating a radiomic model capable of dissecting specific TIME profiles bearing prognostic power in resected NSCLC.

Cytoreductive nephrectomy in the era of targeted- And immuno- therapy for metastatic renal cell carcinoma: An elusive issue? A systematic review of the literature.

Background: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) in the era of targeted- (TT) and immuno- (IT) therapy remains controversial.

Design: The primary objective of the present systematic, performed according to PRISMA guidelines review, was to assess the prevalence of nephrectomy in mRCC patients enrolled in TT/IT randomized phase II/III clinical trials (RCTs) or expanded access programs (EAPs). Medline database was searched from 2003 to 2019 for studies with available nephrectomy data.