scholarly journals Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

2021 ◽  
Vol 11 ◽  
Author(s):  
Pengfei Zhang ◽  
Boxue He ◽  
Qidong Cai ◽  
Guangxu Tu ◽  
Xiong Peng ◽  
...  

BackgroundLung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.MethodsWe analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.ResultsIL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.ConclusionThe IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

2015 ◽  
Vol 25 (9) ◽  
pp. 2532-2540 ◽  
Author(s):  
Xin Jin ◽  
Shao-hong Zhao ◽  
Jie Gao ◽  
Dian-jun Wang ◽  
Jian Wu ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11556-11556
Author(s):  
Marcin Tomasz Skrzypski ◽  
Amelia Szymanowska-Narloch ◽  
Ewa Jassem ◽  
Michał Marczyk ◽  
Joanna Polanska ◽  
...  

11556 Background: Therapies aimed at activation of T and NK cells are developed to expand NSCLC treatments options. It is conceivable that markers of ‘immune ignorant’, ‘immune excluding’ or ‘inflamed’ tumor phenotypes could be prognostic or predictive of benefit from specific immune-targeting therapies. Aim: To assess the prognostic value of expression of T and NK cells mRNA markers and immune-related genes in early stage NSCLC. Methods: qRT-PCR was used to assess 48 mRNAs levels in frozen cancer tissue sections and matched normal lung parenchyma from 56 surgically treated stage I-IIIA NSCLC patients. The mRNA expression (normalized vs. 4 reference genes) was compared between the groups that did (44%) or did not relapse, as well as clinicopathological features (33% never-smokers, 75% lung adenocarcinoma). Results: Low expression of FAS-L (p.adj. = 0.048) , TIGIT and LAG3 was correlated with shorter distant metastasis free survival (DMFS) (p < 0.04). Expression of PD-1 (p = 0.024) and CTLA4 (p = 0.04) was significantly lower in relapsed vs. non-relapsed NSCLCs, whereas there was no difference for PDL-1 and PDL-2. Expression of NK activation markers: NCR3 and NCR1, but not NCR3-ligand 1 was significantly lower in relapsed vs. not relapsed NSCLCs. Other NK cell markers: CD96 and NKG2D were expressed at lower levels (p = 0.02) in relapsed vs. not relapsed NSCLCs, whereas there was no difference for NKG2C and NKG2A. Expression of CXCR3 was lower in relapsed NSCLCs (p = 0.03), however, the expression of its ligands (chemoattractants for lymphocytes) - CXCL9, CXCL10 or CXCL11 or endothelin receptor type B was not different according to metastatic status. GITR and FOXP3 expression was significantly higher in cancers vs. normal lung parenchyma (p.adj. < 0.003). There were no differences in expression according to gender, smoking or NSCLC histological types. Conclusions: Non-inflamed NSCLC phenotype is associated with higher risk of dissemination after primary resection. Neoplastic tissue is characterized by higher level of immune tolerance in comparison to normal lung tissue.


Author(s):  
Haoxuan Wu ◽  
Yang Zhang ◽  
Hong Hu ◽  
Yuan Li ◽  
Xuxia Shen ◽  
...  

2020 ◽  
Vol 9 (7) ◽  
pp. 4204-4211
Author(s):  
Ling Chen ◽  
Hailei Du ◽  
Fangxiu Luo ◽  
Xueyu Chen ◽  
Yong Li ◽  
...  

2018 ◽  
Vol 54 (2) ◽  
pp. 229-234 ◽  
Author(s):  
Tsai-Wang Huang ◽  
Kuan-Hsun Lin ◽  
Hsu-Kai Huang ◽  
Yi-I Chen ◽  
Kai-Hsiung Ko ◽  
...  

2020 ◽  
Author(s):  
Zhiqiang Li ◽  
Hongwei Zheng ◽  
Shanshan Liu ◽  
Xinhua Wang ◽  
Lei Xiao ◽  
...  

Abstract Background: To investigate whether thin-section computed tomography (TSCT) features may efficiently guide the invasiveness basedclassification of lung adenocarcinoma. Methods: Totally, 316 lung adenocarcinoma patients (from 2011-2015) were divided into three groups: 56 adenocarcinoma in situ (AIS), 98 minimally invasive adenocarcinoma (MIA), and 162 invasive adenocarcinoma (IAC) according their pathological results. Their TSCT features, including nodule pattern, shape, pleural invasion, solid proportion, border, margin, vascular convergence, air bronchograms, vacuole sign, pleural indentation, diameter, solid diameter, and CT values of ground-glass nodules (GGN) were analyzed. Pearson’s chi-square test, Fisher’s exact test and One-way ANOVA were adopted tocomparebetweengroups. Receiver operating characteristic (ROC) analysis wereperformedto assess its value for prediction and diagnosis. Results: Patients with IAC were significantly elder than those in AIS or MIA group,and more MIA patients had a smoking history than AIS and IAC. No recurrence happened in the AIS and MIA groups, while 4.3% recurrences were confirmed in the IAC group. As for TSCT variables, we found AIS group showed dominantly higher 91.07%PGGN pattern and 87.50% round/oval nodules than that in MIA and IAC group. In contrast, MIA group showed more cases with undefined border and vascular convergence than AIS and IAC group. Importantly, IAC group uniquely showed higher frequency of pleural invasion compared with MIA and AIS group. The majority of patients (82.1%) in IAC group showed ≥ 50% solid proportion. We found diameter and solid diameter of the lesions were notably larger in the IAC group compared with AIS and MIA groupin quantitative aspect. In addition, for MGGNs, the CT values of ground-glass opacity (GGO) and ground-glass opacity solid portion (GGO-solid) were both higher in the IAC group than AIS and MIA. Finally, we also observed that smooth margin took a dominant proportion in the AIS group while most cases in the IAC group had a lobulate margin. Patients in MIA and IAC group shared higher level of air bronchograms and vacuole signs than AIS group. Conclusions: The unique features in different groups identified by TSCT had diagnosis value for lung adenocarcinoma.


2019 ◽  
Vol 116 (35) ◽  
pp. 17460-17469 ◽  
Author(s):  
Leah Schmidt ◽  
Banu Eskiocak ◽  
Ryan Kohn ◽  
Celeste Dang ◽  
Nikhil S. Joshi ◽  
...  

Natural killer (NK) cells inhibit tumor development in mouse models and their presence in tumors correlates with patient survival. However, tumor-associated NK cells become dysfunctional; thus, stimulation of NK cells in cancer is emerging as an attractive immunotherapeutic strategy. In a mouse model of lung adenocarcinoma, NK cells localized to tumor stroma with immature phenotypes and low functional capacity. To test their responsiveness within established disease, we engineered a system for inducible expression of activating ligands in tumors. After stimulation, NK cells localized inside tumors, with increased cytokine production capacity. Strikingly, T cells were also recruited to tumors in an NK cell-dependent manner, and exhibited higher functionality. In neoantigen-expressing tumors, NK cell stimulation enhanced the number and function of tumor-specific T cells and, in long-term settings, reduced tumor growth. Thus, even in established disease NK cells can be activated to contribute to antitumor immunity, supporting their potential as an important target in cancer immunotherapy.


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