Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival.

Background: Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes.

Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.

Background: Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs.

Methods: The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients.

Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19.

Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer.

Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics.

HUNCHEST-II contributes to a shift to earlier-stage lung cancer detection: final results of a nationwide screening program.

Objectives: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases.

Methods: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening.

Potential subtype-specific therapeutic approaches in small cell lung cancer.

Purpose Of Review: Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients.

Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo.

Pleural mesothelioma (PM) is characterized by poor prognosis and limited therapeutic options. Y-box-binding protein 1 (YB-1) was shown to drive growth and migration of PM cells. Here, we evaluated the effect of genetic and pharmacological targeting of YB-1 on PM growth and response to cisplatin and radiation treatment.

Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair.

Purpose: Acquired chemoresistance is a frequent event in small cell lung cancer (SCLC), one of the deadliest human malignancies. Histone deacetylase inhibitors (HDACi) have been shown to synergize with different chemotherapeutic agents including cisplatin. Accordingly, we aimed to investigate the dual targeting of HDAC inhibition and chemotherapy in SCLC.

Krebs von den Lungen 6 (KL-6) is a novel diagnostic and prognostic biomarker in pleural mesothelioma.

Objectives: Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP).

Unfolding the secrets of small cell lung cancer progression: Novel approaches and insights through rapid autopsies.

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.

Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties.

Comparative expression analysis of immune-related markers in surgically resected lung neuroendocrine neoplasms.

Background: Although immunotherapy has led to a paradigm shift in the treatment of lung cancer, the therapeutic approaches for lung neuroendocrine neoplasms (LNENs) are still limited. Our aim was to explore the immunological landscape and the expression of immune checkpoint markers in LNENs.

Methods: Surgically removed tumor samples of 26 atypical carcinoid (AC), 30 large cell neuroendocrine carcinoma (LCNEC) and 29 small cell lung cancer (SCLC) patients were included.

Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.

Background: No targeted drugs are currently available against small cell lung cancer (SCLC). BCL-2 family members are involved in apoptosis regulation and represent therapeutic targets in many malignancies.

Methods: Expression of BCL-2 family members in 27 SCLC cell lines representing all known four SCLC molecular subtypes was assessed by qPCR, Western blot and mass spectrometry-based proteomics.

YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2.

Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y-box-binding protein-1 (YB-1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB-1 on target gene regulation and PM cell behavior.

Thoracic irradiation as consolidation therapy in patients with extensive-stage small cell lung cancer.

Purpose Of Review: Small cell lung cancer (SCLC) is marked by an exceptionally high proliferative rate and poor prognosis. Given its high propensity to metastasize, nearly two-thirds of SCLC patients are diagnosed with extensive-stage (ES) disease when surgery is not a treatment option anymore. Over several decades, only minimal changes have been made in the therapeutic armamentarium of ES-SCLC.

Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer.

Background: SCLC is an aggressive malignancy where immunotherapies show limited efficacy. We aimed to characterize the SCLC microenvironment according to the expression patterns of SCLC subtype markers and novel immune checkpoints to identify therapeutic vulnerabilities.

Methods: We included SCLC tissue samples from 219 surgically resected, limited-stage patients in this cross-sectional study.

Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study.

The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines.

Clinical relevance of circulating activin A and follistatin in small cell lung cancer.

Objectives: Circulating levels of activin A (ActA) and follistatin (FST) have been investigated in various disorders including malignancies. However, to date, their diagnostic and prognostic relevance is largely unknown in small cell lung cancer (SCLC). Our aim was to evaluate circulating ActA and FST levels as potential biomarkers in this devastating disease.

Wnt Activity and Cell Proliferation Are Coupled to Extracellular Vesicle Release in Multiple Organoid Models.

Extracellular vesicles (EV) are considered as a potential tool for early disease diagnosis; however, factors modifying EV release remain partially unknown. By using patient-derived organoids that capture the cellular heterogeneity of epithelial tissues, here we studied the connection between the Wnt-producing microniche and EV secretion in multiple tissues. Although nearly all cells in pancreatic ductal (PD) and pancreatic ductal adenocarcinoma (PDAC) samples expressed porcupine (PORCN), an enzyme critical for Wnt secretion, only a subpopulation of lung bronchiolar (NL) and lung adenocarcinoma (LUAD) organoid cells produced active Wnt.

EGFR variant allele frequency predicts EGFR-TKI efficacy in lung adenocarcinoma: a multicenter study.

Background: Although lung adenocarcinoma (LADC) with sensitizing mutations of the epidermal growth factor receptor () is highly sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), in most cases disease progression inevitably occurs. Our aim was to investigate the predictive and prognostic significance of adjusted tumoral variant allele frequency (EGFR-aVAF) in the above setting.

Methods: Eighty-nine Caucasian advanced-stage LADC patients with known exon-specific mutations undergoing EGFR-TKI treatment were included.

The landscape of small cell lung cancer metastases: Organ specificity and timing.

Background: Early metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood-borne metastases in a comprehensive large cohort of SCLC patients.