EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth.

The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation, which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARγ in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases proinflammatory immune responses. These results reveal new therapeutic combinations for immunotherapy-resistant EGFR-mutant LUADs and demonstrate how cancer cells can metabolically co-opt TA-AMs through GM-CSF-PPARγ signaling to provide nutrients that promote oncogenic signaling and growth. SIGNIFICANCE: Alternate strategies harnessing anticancer innate immunity are required for lung cancers with poor response rates to T cell-based immunotherapies. This study identifies a targetable, mutually supportive, metabolic relationship between macrophages and transformed epithelium, which is exploited by tumors to obtain metabolic and immunologic support to sustain proliferation and oncogenic signaling.

EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.

The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARγ in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases proinflammatory immune responses. These results reveal new therapeutic combinations for immunotherapy resistant EGFR-mutant LUADs and demonstrate how cancer cells can metabolically co-opt TA-AMs through GM-CSF-PPARγ signaling to provide nutrients that promote oncogenic signaling and growth.

Learning Curve of Real-Time Imaging with C-Arm Based Tomography for Peripheral Lung Nodule Biopsy.

The number of procedures required to attain proficiency with new bronchoscopic biopsy technologies for peripheral pulmonary lesions (PPLs) is uncertain. A prospective, single-center study evaluated learning curves of two operators performing PPL biopsies using a novel, real-time, intraoperative tomographic imaging system in consecutive procedures in adults with CT-detected PPLs. Operators were considered "proficient" when they asked three or fewer questions of the manufacturer's clinical representative with no subsequent navigations in which they asked more than three questions. A total of 31 procedures were performed on 31 patients (Operator 1: 18, Operator 2: 13). Proficiency was achieved after an average of 10 procedures (Operator 1: 12, Operator 2: 8). From the learning curve to the post-learning curve period, the number of questions (median [IQR]: 23 [9.5-41.5] versus 0 [0-1], p < 0.001) and radiation dose (median [IQR]: 19.5 mGy/m2 [1.9-43.5] versus 1.5 mGy/m2 [0.7-3.3], p = 0.05) decreased significantly; procedure time decreased (median [IQR]: 12 min [7-20] versus 8 min [3-15], p = 0.29); and diagnostic yield increased significantly (13/20 cases [65%] to 11/11 cases [100%]), (p = 0.03). Based on this unique, clinically relevant method of assessing learning curve, proficiency with the Body Vision system was achieved at approximately the tenth procedure. These findings require validation in larger, diverse populations.

Diagnosis of systemic lupus erythematosus with early manifestation of an eosinophilic pleural effusion.

A woman in her 70s with a history of Crohn's disease presented to the emergency department with dyspnoea, cough and intermittent fevers. Evaluation revealed a pleural effusion with neutrophil predominance, and initial suspicion of infection prompted a short course of antibiotic therapy. However, the patient subsequently developed recurrent pleural effusion with eosinophilic predominance. Serological data confirmed a diagnosis of systemic lupus erythematosus (SLE) and the patient was started on appropriate treatment.This case presents an initial manifestation of eosinophilic-dominant pleural effusion in SLE. Current guidelines in treating pleural effusions do not explore rheumatological causes. However, we believe that our case demonstrates the value of a prompt investigation for rheumatological aetiologies in an otherwise unclassified eosinophilic-predominant pleural effusion. Such an investigation should include serological data as an important confirmatory marker for the diagnosis of SLE.

Narrative review of tools for endoscopic ultrasound-guided biopsy of mediastinal nodes.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) has revolutionized the diagnosis and staging of lung cancer. Multiple studies support EBUS as a safe, cost-effective, and accurate method of diagnosing lung cancer. Even with the groundbreaking developments of immunotherapy and targeted therapy in advanced non-small cell lung cancer, EBUS-TBNA remains the optimal method for obtaining tissue for molecular testing. Since the advent of EBUS, there have been a multitude of needles and biopsy tools that have been developed, each with its own unique features that may make it suitable for various clinical situations. With needle sizes ranging from 19 gauge to 25 gauge, and both aspiration and biopsy needles, as well as mini-forceps available, there are now numerous tools to choose from. Over the past several years, EBUS has also gained new roles outside the realm of lung malignancy. EBUS now plays an important role in diagnosing other thoracic pathology, such as sarcoidosis and lymphoma, as well as facilitating treatment of both benign and malignant disease. As the use of EBUS has become more widespread, new tools have emerged to allow for EBUS to continue expanding its applicability. This review examines the evidence for the current equipment and novel tools that are being used in EBUS-guided biopsy.

Cone beam navigation bronchoscopy: the next frontier.

Navigation bronchoscopy has reached a new horizon in its evolution. Combining with real-time imaging modalities, such as cone-beam computed tomography (CBCT) and augmented fluoroscopy (AF), navigation success can finally be confirmed with high degree of accuracy in real-time. With utilization of this modality, additional clinical observations are being made to help address the CT-body divergence problem and further improve navigation accuracy. This review focuses on description of CBCT navigation technique, provide tips on addressing CT-Body divergence, and review evidence for CBCT applications in navigation bronchoscopy.