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Background: Genomic testing gives guidance to the treatment options in lung adenocarcinoma patients, but some patients are unable to obtain tissue samples due to lesion location or intolerance. Cell-free circulating tumor DNA (ctDNA) tested in plasma or pleural effusion is an advanced access to solve the problem. Our study descriptively identified the genetic variations of advanced Chinese lung adenocarcinoma patients and analyzed the overall survival of patients with EGFR mutations., Methods: A total of 152 patients' plasma samples were included, and gene mutations were detected by NGS using an Illumina Miseq tabletop sequencer., Results: Frequencies of altered were EGFR 46.05%, ALK 7.24%, KRAS 6.58%, PIK3CA 6.58%, PTEN 2.63%, HER2 1.97%, MET 1.97%, BRAF 1.32%, NF1 1.32%, and ROS1 0.66%. We identified 48 cases with double or triple driver gene mutations. Multiple mutations were more frequently observed in EGFR and PIK3CA genes. Patients harboring coexistent mutations with an EGFR mutation tended to have a shorter overall survival than those with exclusively EGFR mutations., Conclusion: EGFR, ALK, and KRAS were common driver gene in Chinese patients with stage IV lung adenocarcinoma. Multiple mutations were detected in the ctDNA samples and involve more EGFR and PIK3CA mutations. The existence of coexisting gene mutations may have adverse effects on the prognosis of patients with EGFR mutation. The unknown mutations discovered by NGS may provide new targets for gene targeting therapy, and ctDNA test by NGS is an effective method for making appropriate treatment choices., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Songchen Zhao et al.)

There are significant differences in pathology, etiology, clinical features, and treatment options between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). However, the differences of macrophage distribution and its associated function between SCLC and NSCLC are not fully investigated. Through methods of flow cytometry and cytometric bead array, we examined the levels of various subtypes of macrophages, monocytes, and regulatory T cells (Tregs) as well as interleukin (IL)-10 in bronchoalveolar lavage fluid (BALF) of patients with SCLC or NSCLC. Our study showed that the frequency of CD14+, CD206+CD14+ and IL-10+CD206+CD14+M2-like macrophages were significantly increased, with simultaneously elevated IL-10 in BALF of SCLC patients, as compared to those in BALF of NSCLC patients. Furthermore, the increased frequency of IL-10+CD206+CD14+M2-like macrophages and elevated level of IL-10 in BALF of SCLC patients were positively correlated with advanced tumor stage, but negatively correlated with their survival time. On the other hand, the level of supernatant IL-10 and frequency of IL-10+CD206+CD14+M2-like macrophages in SCLC patients were positively correlated. The frequency of above mentioned macrophages was also positively correlated with that of Foxp3+CD25+CD4+Tregs. Compared to NSCLC patients, the level of circulating IL-10+CD206+CD14+M2-like monocytes in SCLC patients were significantly increased after chemotherapy. Overall, increased IL-10+CD206+CD14+M2-like macrophages were an important feature of SCLC, rather than NSCLC, and it is associated with development of SCLC.

The present study was designed to evaluate the percentage of different programmed cell death-1 (PD-1) + T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD-1 + T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD-1 + T cell subsets. These present results revealed that the percentage of circulating PD-1 + Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non-small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD-1 + Tfh cells were also significantly enhanced in patients in the extensive-stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD-1 + Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD-1 + Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL-2 and IFN-γ derived from PD-1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD-1 + T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target., (© 2019 John Wiley & Sons Australia, Ltd.)

Purpose: CD4 + CD25 + Foxp3 + regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4 + CD25 - Foxp3 + Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4 + CD25 - Foxp3 + Treg cells and their role in NSCLC. Methods: The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. Results: The frequencies of circulating CD4 + CD25 + T cells and CD4 + CD25 + Foxp3 + and CD4 + CD25 - Foxp3 + Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4 + CD25 + Foxp3 + and CD4 + CD25 - Foxp3 + Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4 + CD25 - Foxp3 + Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4 + CD25 - Foxp3 + Treg cells and CD14 + monocytes in vitro resulted in a higher frequency of CD206 + CD14 + M2-like monocytes compared with CD14 + monocytes. Conclusions: Elevated circulating CD4 + CD25 - Foxp3 + Treg cells may be involved in the pathogenesis of NSCLC.