Background: Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Methods: Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Results: Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm²) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm²) and stroma (approximately 34/mm²) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm²) and stroma (13/mm²) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma were positively associated with patient's survival time in a univariate analysis (P < 0.01 or 0.001). In a multivariate Cox proportional hazards analysis, the M1 macrophage density in the tumor islets was an independent predictor of patient's survival time. Conclusions: The M1 macrophage density in the tumor islets is an independent predictor of survival time in NSCLC patients.

Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.

Background: Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. Methods: Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0). Results: The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time. Conclusions: The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.

The goal of this study was to assess the impact of a preoperative 1-week, systematic, high-intensity inpatient exercise regimen on patients with lung cancer who had risk factors for postoperative pulmonary complications (PPCs). We conducted a randomized controlled trial with 101 subjects of a preoperative, 7-day systematic, integrated, high-intensity pulmonary exercise regimen. The control group received standard preoperative care. We analysed the occurrence of PPCs in both groups as the primary outcome; other outcomes included changes in blood gas, quality of life, peak expiratory flow rate, the 6-min walk distance and others. The 6-min walk distance showed an increase of 22.9 ± 25.9 m in the intervention group compared with 4.2 ± 9.2 m in the control group, giving a between-group difference of 18.7 m (95% confidence interval: 8.8–28.6; P < 0.001); the peak expiratory flow increased by 25.2 ± 24.6 l/min, compared with 4.2 ± 7.7 l/min (between-group difference: 21.0 m, 95% confidence interval: 7.2–34.8; P = 0.003). The intervention group had a shorter average total (15.6 ± 3.6 vs 17.7 ± 5.3 days, P = 0.023) and postoperative length of stay (6.1 ± 3.0 vs 8.7 ± 4.6 days, P = 0.001) than the control group; the incidence of PPCs (9.8%, 5/51 vs 28.0%, 14/50, P = 0.019) was significantly lower. A multivariable analysis of the risk of PPCs identified short-term rehabilitation intervention to be an independent risk factor (odds ratio = 0.156, 95% confidence interval: 0.037–0.649, P = 0.011). The study results suggested that a systematic, high-intensity pulmonary exercise programme was a practical strategy when performed preoperatively in patients with lung cancer with risk factors for PPCs. ChiCTR-IOR-16008109.