Anti-PD1 based precision induction therapy in unresectable stage III non-small cell lung cancer: a phase II umbrella clinical trial.

The efficacy and safety of induction-immunotherapy followed by surgery for unresectable Stage III non-small cell lung cancer (NSCLC) remain challenging. In this open-label, single-center, phase II clinical umbrella trial (ChiCTR2000035367), 100 unresectable Stage III NSCLC patients are enrolled. Patients with PD-L1 expression ≥ 50% but contraindications to anti-angiogenic therapy receive immuno-monotherapy.

Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The integrative development of machine learning-based models reveals a random survival forest (RSF) prognostic model for LUSC.

Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer.

Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB-chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis.

Enhancing the differential diagnosis of small pulmonary nodules: a comprehensive model integrating plasma methylation, protein biomarkers, and LDCT imaging features.

Background: Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5-10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules.

Methods: Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention.

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate.

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center.

Background: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) exhibited a higher propensity for lymph node metastasis (LNM). This study aimed to investigate risk factors of occult lymph node metastasis (OLNM) and recurrence in resectable ALK-rearranged NSCLC patients.

Methods: This retrospective analysis included patients with ALK-rearranged NSCLC receiving lung resections at Shanghai Pulmonary Hospital from June 2016 to August 2021.

Spread Through Air Spaces in Stage I Pulmonary Large Cell Neuroendocrine Carcinoma.

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents an exceptionally aggressive and infrequent variant within the realm of non-small cell lung cancer, necessitating surgical intervention as the primary therapeutic approach. However, the postoperative management strategy for early-stage patients continues to be a subject of intense debate and uncertainty.

Methods: A retrospective analysis was conducted on a cohort of patients diagnosed with LCNEC who underwent surgical resection at Shanghai Pulmonary Hospital between July 2018 and June 2022.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified.

The impact of oncogenic driver mutations on neoadjuvant immunotherapy outcomes in patients with resectable non-small cell lung cancer.

Background: Neoadjuvant immunotherapy has been demonstrated to be effective and safe in resectable non-small cell lung cancer (NSCLC) patients. However, the presence of different oncogenic driver mutations may affect the tumor microenvironment and consequently influence the clinical benefit from immunotherapy.

Methods: This retrospective study included consecutive NSCLC patients (stage IIA to IIIB) who underwent radical surgery after receiving neoadjuvant immunotherapy at a single high-volume center between December 2019 and August 2022.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily).

Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing.

Background: Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored.

Methods: We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8).

The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center.

Background: The effectiveness of segmentectomy for stage IA lung adenocarcinoma (IA-LUAD) has been well-documented. However, the efficacy and safety of wedge resection for peripheral IA-LUAD remains controversial. This study evaluated the feasibility of wedge resection in patients with peripheral IA-LUAD.

The efficacy of neoadjuvant -TKI therapy combined with radical surgery for stage IIIB lung adenocarcinoma harboring mutations: A retrospective analysis based on single center.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (-TKIs) could provide survival benefits for locally advanced -mutant (m) non-small cell lung cancer (NSCLC). However, the role of radical surgery for -TKI treated stage IIIB m NSCLC remains controversial. This study attempted to assess the feasibility of neoadjuvant -TKI followed by radical surgery for stage IIIB m NSCLC.

Single-Cell Transcriptome Identifies Drug-Resistance Signature and Immunosuppressive Microenvironment in Metastatic Small Cell Lung Cancer (Advanced Genetics 2/03).

Single-Cell RNA Sequencing This cover illustrates the work of Xujun Wang, Xianmin Zhu, Peng Zhang, and co-workers in article number 2100060 which reveals the drug-resistance signature and immunosuppressive microenvironment in small cell lung cancer (SCLC) by single-cell RNA-sequencing. "Wu Song Fought the Tiger" comes from the famous Chinese novel: Outlaws of the Marsh. In the cover, the warrior Wu Song stands for the doctors and researchers.

Single-Cell Transcriptome Identifies Drug-Resistance Signature and Immunosuppressive Microenvironment in Metastatic Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a deadly neuroendocrine malignancy with high metastasis. However, the heterogeneity of metastatic SCLC at the single-cell level remains elusive. The single-cell transcriptome of a total of 24 081 cells in metastatic lymph node samples from seven SCLC patients via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is examined.

Significance of spread through air spaces in small cell lung cancer.

Purpose: Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). Nevertheless, little is known about the role of STAS in small cell lung cancer (SCLC). We sought to determine whether STAS has a significant effect on recurrence among SCLC patients.

Tertiary lymphoid structure and decreased CD8 T cell infiltration in minimally invasive adenocarcinoma.

Knowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4 T cell infiltration, high B-cell activation, and low CD8 T cell infiltration.

Correction: RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.

[This corrects the article DOI: 10.1371/journal.ppat.

Identification of an Individualized Metabolism Prognostic Signature and Related Therapy Regimens in Early Stage Lung Adenocarcinoma.

Objective: The choice of adjuvant therapy for early stage lung adenocarcinoma (LUAD) remains controversial. Identifying the metabolism characteristics leading to worse prognosis may have clinical utility in offering adjuvant therapy.

Methods: The gene expression profiles of LUAD were collected from 22 public datasets.

Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response.

Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi-Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from , suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity.