Regarding the participation of RUNX1 in lung cancer, we investigated its mechanism in regulating M2 polarization of tumor-associated macrophages in lung cancer. The extracted bone marrow cells were differentiated into macrophages (BMDMs), followed by tumor-conditioned medium (CM) stimulation to simulate the impact of tumor cells on macrophages in vivo, and treatment with RUNX1 shRNA, or pCDNA3.1-ACP5 and SIS3. Macrophage polarization and cytokine secretion were assessed by flow cytometry and ELISA, followed by evaluations of RUNX1, ACP5, p-β-catenin, β-catenin and p-SMAD3 levels. The ACP5-β-catenin interaction was detected by Co-IP. BMDMs were co-cultured with Lewis lung carcinoma cells using Transwell. The malignant behaviors of cells were assessed by CCK-8 and Transwell assays. In vivo experiments were conducted to verify roles of RUNX1. Tumor-CM stimulated BMDM M2 polarization. RUNX1 was up-regulated in tumor-CM-stimulated macrophages and M2-type BMDMs, and was poorly expressed in M1-type BMDMs. RUNX1 knockdown induced M1 marker expression and reduced M2 marker expression, and repressed non-small cell lung cancer (NSCLC) cell malignant behaviors. The effects of RUNX1 silencing were partly abrogated by ACP5 overexpression. ACP5 interacted with β-catenin to promote SMAD3 phosphorylation. Downregulation of SMAD3 phosphorylation partially reversed tumor-CM-promoted BMDM M2 polarization and NSCLC cell malignant behaviors. RUNX1 promoted M2 polarization and NSCLC cell malignant behaviors by promoting ACP5-mediated SMAD3 phosphorylation. RUNX1 knockdown inhibited M2 polarization in LLC mice to suppress tumor growth in vivo. RUNX1 promoted BMDM M2 polarization by facilitating the interaction between ACP5 and β-catenin to elevate SMAD3 phosphorylation, thus promoting NSCLC progression.

BACKGROUND:The interaction between tumor cells and tumor microenvironment is a necessary condition for promoting the metastasis of malignant tumors. METHODS:Two different transwell culture systems were interfered with by recombinant factor placental growth factor (re-PIGF) and the re-PIGF + transforming growth factor-β1 (TGF-β1)-neutralizing antibody (anti-TGF-β1). We performed immunofluorescence, flow cytometry and enzyme linked immunosorbent assay (ELISA) to analyze the expression of PIGF, fms-like tyrosine kinase-1 (Flt-1), macrophage marker F4/80 +, macrophage M2 marker CD163+ and TGF-β1 in vitro. Meanwhile, cell viability assay and optical microscope assay were conducted to explore the cell viability and vascularization ability of human umbilical vein endothelial cells (HUVECs). RESULTS:Re-PIGF increased the expression of PIGF in A549 cells and the expression of Flt-1 in BM-Mac cells, and significantly enhanced the ability of bone marrow-derived macrophages (BM-Mac) to transform into macrophages. At the same time, re-PIGF increased the expression of cytokine TGF-β1 in A549 cells/BM-Mac transwell culture system. On the contrary, re-PIGF + anti-TGF-β1 inhibited the expression of Flt-1 in BM-Mac cells and inhibited the ability of BM-Mac cells to transform into macrophages. Finally, re-PIGF + anti-TGF-β1 reduced the cell viability and angiogenesis of HUVECs. CONCLUSION:The surface molecule PIGF of lung cancer cells could bind to the receptor Flt-1 on the surface of macrophages, thereby increasing the production of TGF-β1, and ultimately promoting the formation of angiogenesis in lung cancer.

Brain metastases are the most common distant metastases of non-small-cell lung adenocarcinoma; however, few effective treatment options are available. Cytotoxic T lymphocytes are effective in lysing tumor cells, which is the basis of current T-cell immunotherapy. We report 3 cases of non-small-cell lung adenocarcinoma with brain metastases in which adoptive T-cell transfer therapy achieved the desired results. (C) 2020 Elsevier Inc. All rights reserved.

Although surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post-ablation complications.

Objective To investigate the effects of radiofrequency ablation (RFA) on CD4 + T-cell subsets in lung cancer patients and its significance.Methods Forty-five patients who underwent RFA were selsected at Peking University Shenzhen Hospital from May 2015 to March 2016.CD4 + T-cell subsets in the peripheral blood were detected.Differences in CD4 + T-cell subsets before and after RFA were compared.The relationships between changes in CD4 + T-cell subsets and clinicopathologic characteristics and therapeutic effectiveness were analyzed.Results The Thl cell level and Thl/Th2 cell ratio significantly increased at 2 weeks after RFA than before RFA and the levels of Th2,Thl7 and Treg significantly declined (all P ＜ 0.05).Significant differences were found in changes of CD4 + T-cell between patients with stage Ⅰ/Ⅱ lung cancer,Karnofsky performance status (KPS) ≥ 60 and ablation volume ≥70％ and patients with stage Ⅲ/Ⅳ lung cancer,KPS score ＜60 and ablation volume ＜70％ (all P ＜ 0.05).Conclusion After RFA,anti-tumor immune response was improved.Changes in CD4 + T-cell subsets can be considered as one of the factors in predicating the efficacy of RFA and the prognosis in lung cancer patients.

Aims: To analyze the changes of CD4+T-cell subsets following radiofrequency ablation (RFA) in lung cancer and the impact of RFA on the antitumor immunity. Subjects and Methods: Flow cytometry was employed to detect CD4+T-cell subsets in the peripheral blood from 45 healthy controls and 45 lung cancer patients before and after RFA. The correlation between CD4 +T-cell subsets and the clinical characteristics was discussed by comparing the results between different groups. Results: Compared with the healthy controls, the lung cancer patients showed a decline in Th1 cells, but higher Th2, Th17, and Treg cells (P < 0.05). Th1 cell level and Th1/Th2 cell ratio were significantly lower for stage III/IV than Stage I/II and also lower for patients with Karnofsky Performance Status (KPS) score <60 than ≥ 60 (P < 0.05). The levels of Th2, Th17, and Treg cells were much higher for patients with Stage III/IV and KPS score <60 (P < 0.05). After 2 weeks of RFA, the level of Th1 cells and Th1/Th2 cell ratio increased, while the levels of Th2, Th17, and Treg cells declined (P < 0.05). For lesions with ablation volume ≥ 70%, the level of Th1 cells and Th1/Th2 cell ratio increased, whereas the levels of Th2, Th17, and Treg cells declined dramatically (P < 0.05). Conclusions: The level of Th1 cells declined in lung cancer patients, especially for patients with Stage III/IV and KPS score <60. After RFA, the level of Th1 cells and Th1/Th2 increased, whereas the levels of Th2, Th17, and Treg cells declined, indicating an improvement of antitumor immunity. The changes were more prominent for lesions with ablation volume ≥ 70%.

The application of radiofrequency ablation in malignant tumor is a new technique in tumor targeted therapy in recent years.Radiofrequency ablation of malignant tumor can enhance the cellular immune function of the patients by changing T lymphocyte subsets,which may be one of the mechanisms in tumor therapy and affects the prognosis of malignant tumor.