IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.

Development and validation of a clinical decision tool for preoperative micropapillary and solid pattern lung adenocarcinoma of CT≤2 cm.

BACKGROUND: Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients. METHODS: For this retrospective study, the presence of MP and/or S was evaluated in 2167 consecutive patients who underwent surgical resection for clinical stage IA1-2 lung adenocarcinoma. MP and/or S pattern-positive patients and negative-pattern patients were matched at a ratio of 1:3. The Lasso regression model was used for data dimension reduction and imaging signature building. Multivariate logistic regression was used to establish the predictive model, presented as an imaging nomogram. The performance of the nomogram was assessed based on calibration, identification, and clinical usefulness, and internal and external validation of the model was conducted. RESULTS: The proportion of solid components (PSC), Sphericity, entropy, Shape, bronchial honeycomb, nodule shape, sex, and smoking were independent factors in the prediction model of MP and/or S lung adenocarcinoma. The model showed good discrimination with an area under the ROC curve of 0.85. DCA demonstrated that the model could achieve good benefits for patients. RCS analysis suggested a significant increase in the proportion of MP and/or S from 11% to 48% when the PSC value was 68%. CONCLUSION: Small MP and/or S adenocarcinoma can be effectively identified preoperatively by their typical 3D and 2D imaging features.

Computed tomography imaging and clinical characteristics of pulmonary ground-glass nodules ≤2 cm with micropapillary pattern.

BACKGROUND: The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground-glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. METHODS: A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground-glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. RESULTS: Different pathological subtypes of mGGN differed in morphological features (p < 0.05). The rate of lymph node metastasis was significantly higher in micropapillary mGGNs than in nonmicropapillary mGGNs. In the TCGA database samples, lactate transmembrane protein activity, collagen transcription score, and fibroblast EMT score were remarkably higher in micropapillary adenocarcinoma. Other pathological subtypes had a better survival prognosis and longer disease-free survival compared with micropapillary adenocarcinoma. CONCLUSION: mGGNs ≤2 cm with a micropapillary pattern have a higher risk of lymph node metastasis compared with SNs, and computed tomography (CT) imaging features can assist in their diagnosis.

Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT.

Blood vessel passage on CT exerts a vital part in early diagnosis as well as treatment of carcinoma of the lungs. Intratumoral microvascular density (iMVD) has gradually become the focus of research on biological behavior, appearance, and evolution of malignant tumors nowadays. The aim of this paper was to verify whether there is a correlation between the iMVD and the vascular morphology of ground glass nodules (GGNs). A total of 109 patients with pulmonary GGN were classified into three groups (I,II, and III) according to the vascular morphology on CT, and their expression of CD31-, CD34-, and CD105-labeled iMVD was detected by the streptoavidin-biotin method, statistically analyzing the iMVD values of each group. The expression of CD31, CD34, and CD105 in different lung tissues was significantly different, with remarkably higher iMVD in lung cancer tissues than in adjacent normal lung tissues. In the imaging sort of types I, II, and III according to the means of vascular passage, the iMVD expression of CD31, CD34, and CD105 was significantly different between groups. These data suggest that the presence and the abnormal morphology of vessels seen within GGNs indicate the occurrence and progression of lung cancer in pathology. It offers a strong theoretical foundation for early diagnosis of carcinoma of the lungs, thus providing a more precise clinical diagnosis and prognosis of early-stage lung cancer.

The arterial-ligation-alone method for identifying the intersegmental plane during thoracoscopic anatomic segmentectomy.

BACKGROUND: Currently, methods for identifying the intersegmental plane during anatomical segmentectomy can be classified into 2 categories: the bronchial method and the vascular method. One of the vascular methods, the arterial-ligation-alone method, has not yet been validated or objectively evaluated in a large case series. We thus aimed to confirm that the arterial-ligation-alone method could effectively and accurately identify the intersegmental plane. METHODS: We retrospectively reviewed the records of 104 patients who were scheduled for thoracoscopic anatomic segmentectomy. Preoperative three-dimensional (3D) reconstruction was performed on all the affected lungs to distinguish the targeted segmental arteries, veins and bronchi. The procedure was as follows: first, based on the 3D reconstruction of the lung, the targeted segmental arteries were distinguished and ligated. Second, bilateral pulmonary ventilation was performed with pure oxygen. When the affected lung had completely inflated, contralateral pulmonary ventilation was performed. After waiting for some time, the first intersegmental plane could be obtained, and the time was recorded as T1, with an electric coagulation hook being used for marking. Thirdly, when the targeted segmental veins and bronchi had been ligated, the second intersegmental plane could be obtained by the inflation-deflation method as before, with the waiting time being recorded as T2. The differences between the 2 intersegmental planes were evaluated by 2 experienced chief thoracic surgeons. RESULT: In a total of 99 (95.2%) patients, the intersegmental planes were successfully and accurately identified by the arterial-ligation-alone method. Ultimately, 85 (81.7%) patients underwent thoracoscopic anatomic segmentectomy. The results for evaluating the differences between the 2 planes were as follows: completely consistent (94 cases, 94.9%), basically consistent (5 cases, 5.1%), and discrepant (0 cases, 0%). The mean T1 was 13.6±2.7 minutes (range, 8-25 minutes), and the mean T2 was 13.0±2.6 minutes (range, 8-23 minutes), with P=0.100 (95% CI). For 99 patients, the mean nodule size was 1.1±0.34 cm. In the 85 patients who underwent segmentectomy, the mean margin width was 2.84±0.51 cm, the mean operative duration was 165.6±18.3 minutes, the mean operative hemorrhage was 52.1±20.2 mL, and the mean duration of chest tube drainage was 3.9±1.3 days. Postoperative complications related to operative procedures occurred in 2 cases. CONCLUSIONS: The arterial-ligation-only method can effectively, accurately and inexpensively identify the intersegmental plane, and is especially suitable for the patients whose veins or bronchi are difficult to anatomize. Whether the target bronchus is ligated has no effect on the intersegmental plane.

Curative effect comparison between Ivor-Lewis esophagectomy and left transthoracic esophagectomy in treatment of middle thoracic esophagus carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare and evaluate the therapeutic efficacy of Ivor-Lewis esophagectomy and one incision esophagectomy through left thoracic and above aortic arch anastomosis approach (left transthoracic esophagectomy) in order to choose a proper surgical procedure to treat middle esophageal carcinoma. METHODOLOGY: Patients who underwent Ivor-Lewis esophagectomy (n=132) and who underwent left transthoracic esophagectomy (n=52) between January 2003 and June 2005 were included. The survival rate was calculated by Kaplan-Meier method and the prognostic risk factors were assessed by Cox regression analysis. RESULTS: Postoperative complications occurred in 43 patients (23.4%), with 31 patients (23.5%) and 12 patients (23.1%) in the Ivor-Lewis group and in the left transthoracic esophagectomy group, respectively. The overall 5-year survival rate was 36.4%, with 37.1% and 34.6% in the Ivor-Lewis group and in the left transthoracic esophagectomy group, respectively (p>0.05). In Cox regression analysis, T classification (HR=1.43, p=0.025) and N classification (HR=1.76, p=0.004) were the independent prognostic risk factors. CONCLUSIONS: Ivor-Lewis esophagectomy and left transthoracic esophagectomy are both feasible options to treat middle thoracic esophageal squamous cell carcinoma. Patients' individual condition is suggested to be taken into account when choosing the operative approach.