Feature Engineering Assessment of Tumor Infiltrating Lymphocytes in Lung Adenocarcinoma.

Tumor-Infiltrating Lymphocytes (TIL) are emerging as immunotherapy prognostic markers. Currently, TIL are assessed on hematoxylin and eosin (H&E)-stained slides of tumor tissue by pathologists. This approach is time-consuming, and subjected to inter-observer variability.

IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells.

IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human mucosal-associated invariant T (MAIT), but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells.

Unraveling the link between cholesterol and immune system in cancer: From biological mechanistic insights to clinical evidence. A narrative review.

Cholesterol and its metabolism seem to be involved not only in cancer progression but also in immune cells activity. In this comprehensive review, we summarize preclinical, translational, and clinical evidence regarding the crucial role of cholesterol and its metabolism in regulating the immune response against cancer cells, shedding light on the multifaceted mechanisms by which cholesterol influences immune cell function and anti-tumor immunity. By synthesizing findings from preclinical studies, we have elucidated the impact of cholesterol on immune cell activation, differentiation, and effector functions.

Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.

Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y.

Case report: Single gene testing and comprehensive genomic profiling in non-small cell lung cancer-a case series of divergent results from a large reference laboratory.

Clinical management of non-small cell lung cancer (NSCLC) requires accurate identification of tumor-specific genetic alterations to inform treatment options. Historically, providers have relied on single-gene testing (SGT) for actionable variants due to a perception of cost-effectiveness and/or efficient turnaround time compared to next-generation sequencing (NGS). However, not all actionable variants may be evaluated through SGT modalities, and an SGT approach can exhaust valuable tissue needed for more comprehensive analyses.

Biomarkers in head and neck squamous cell carcinoma: unraveling the path to precision immunotherapy.

Recent strides in understanding the molecular underpinnings of head and neck cancers have sparked considerable interest in identifying precise biomarkers that can enhance prognostication and enable personalized treatment strategies. Immunotherapy has particularly revolutionized the therapeutic landscape for head and neck squamous cell carcinoma, offering new avenues for treatment. This review comprehensively examines the application and limitations of the established and emerging/novel biomarkers for head and neck squamous cell carcinoma.

scConfluence: single-cell diagonal integration with regularized Inverse Optimal Transport on weakly connected features.

The abundance of unpaired multimodal single-cell data has motivated a growing body of research into the development of diagonal integration methods. However, the state-of-the-art suffers from the loss of biological information due to feature conversion and struggles with modality-specific populations. To overcome these crucial limitations, we here introduce scConfluence, a method for single-cell diagonal integration.

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.

Molecular mechanisms reconstruction from single-cell multi-omics data with HuMMuS.

Motivation: The molecular identity of a cell results from a complex interplay between heterogeneous molecular layers. Recent advances in single-cell sequencing technologies have opened the possibility to measure such molecular layers of regulation.

Results: Here, we present HuMMuS, a new method for inferring regulatory mechanisms from single-cell multi-omics data.

Microglia maintain structural integrity during fetal brain morphogenesis.

Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease.

Neoadjuvant therapy in hormone Receptor-Positive/HER2-Negative breast cancer.

Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making.

Paired single-cell multi-omics data integration with Mowgli.

The profiling of multiple molecular layers from the same set of cells has recently become possible. There is thus a growing need for multi-view learning methods able to jointly analyze these data. We here present Multi-Omics Wasserstein inteGrative anaLysIs (Mowgli), a novel method for the integration of paired multi-omics data with any type and number of omics.

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed.

Materials And Methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes.

Results: At a median follow-up of 32.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED).

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.

How to manage G12C-mutated advanced non-small-cell lung cancer.

Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common alteration. Although mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations.

The Landscape of ALK-Rearranged Non-Small Cell Lung Cancer: A Comprehensive Review of Clinicopathologic, Genomic Characteristics, and Therapeutic Perspectives.

During the last decade, the identification of oncogenic driver mutations and the introduction of tyrosine kinase inhibitors (TKIs) in daily clinical practice have substantially revamped the therapeutic approach of oncogene-addicted, non-small cell lung cancer (NSCLC). Rearrangements in the anaplastic lymphoma kinase (ALK) gene are detected in around 3-5% of all NSCLC patients. Following the promising results of Crizotinib, a first-generation ALK inhibitor (ALK-i), other second-generation and more recently third-generation TKIs have been developed and are currently a landmark in NSCLC treatment, leading to a significant improvement in patients prognosis.

Management of lung cancer patients during COVID-19 pandemic: dos, don'ts and don't knows.

Aim: During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the virus between patients and healthcare professionals on the other hand. Due to the pandemic's unpredictable duration, physicians had to evaluate the risk/benefit ratio of anti-cancer therapeutic strategy to do the best for their patients and to protect patients themselves, as well as healthcare workers.

Methods: Systematic literature research was performed with the aim to assess the available guidelines for the management of lung cancer patients during the COVID-19 pandemic.

Rising incidence of late stage breast cancer after COVID-19 outbreak. Real-world data from the Italian COVID-DELAY study.

Purpose: Breast cancer (BC) patients' (pts) management was affected by a global reorganization after Coronavirus disease 2019 (COVID-19). Our multicenter study aimed to assess the impact of COVID-19 on access to diagnosis, staging and treatment for BC pts compared to pre-pandemic.

Methods: Medical records of all consecutive newly diagnosed BC pts referred to 6 Italian Institutions between March and December 2020 were assessed.

Advanced non-small-cell lung cancer: how to manage and exon 20 insertion mutation-positive disease.

exon 20 insertion mutations (Ex20ins) and 2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and 2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.

Non-small-cell lung cancer: how to manage -mutated disease.

The treatment of non-small-cell lung cancer (NSCLC) harbouring mutations has witnessed some major breakthroughs in the last years. On the one hand, the recent advent of the third-generation tyrosine kinase inhibitor (TKI) osimertinib has reshaped the therapeutic algorithm both in the first-line and adjuvant settings for patients with common activating Ex19del and L858R mutations. On the other hand, the availability of new comprehensive next-generation sequencing panels, to be used on tumour tissue or on liquid biopsy, has revealed the existence of uncommon as well as compound mutations that partially explain the onset of resistance.

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma.

Purpose: Lurbinectedin is a promising new drug being investigated in pre-treated patients with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). Its clinical activity in the real-world setting has not been investigated yet.

Patients And Methods: Clinical data of patients with SCLC and MPM who were treated with lurbinectedin were prospectively collected.

Alarming Drop in Early Stage Colorectal Cancer Diagnoses After COVID-19 Outbreak: A Real-World Analysis from the Italian COVID-DELAY Study.

Background: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter Italian study aimed to evaluate whether COVID-19 has impacted access to diagnosis, staging, and treatment for patients newly diagnosed with colorectal cancer (CRC), compared with pre-pandemic time.