Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung

Abstract

Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma. Moreover, here we found increased IL6R in the tumour free part of the lung. By using a murine model of lung adenocarcinoma, we discovered that few lung tumour cells expressed IL-6R and CD4+CD25+Foxp-3+ T regulatory cells down-regulated IL-6R in the tumour bearing lungs. Downstream of IL-6R, the Th17 lineage-specification factors: Signal transducer and activator of transcription 3 (STAT3), Basic leucine zipper transcription factor, BATF and a protein encoded by the RORC in human (RAR-related orphan receptor C) (RORγT), were also found induced in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to those carrying squamous cell carcinoma. Moreover, pSTAT3 protein was found phosphorylated and auto-phosphorylated in the tumoural region of patients with adeno cell carcinoma of the lung as compared to the tumoural region of patients with squamous cell carcinoma of the lung. Intranasal application of anti-IL-6R antibodies in a murine model of lung adenocarcinoma, induced T regulatory cell markers such as Foxp3, Ctla4, Icos, Il10, Il21, Folr4 and Lag3 and inhibited Rorc in lung adenocarcinoma.

Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database

“…This immune evasive mechanism has been known to be hijacked by many kinds of tumors, including NSCLC, where upregulation of the immune checkpoint axis has been reported. 6,28 Although clinical trials with immune checkpoint inhibitors showed promising results, not all patients have been benefited and the need of patient selection for personalized treatment is being advocated. Recent data showed that patients with upregulation of the immune checkpoint axis before treatment may have higher response.…”

The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma

“…Most of the material and methods related to the human studies where recently reported in details. 3,35,36,45,46 Total cells isolation from human lung samples Samples were cut into very small pieces using scalpels (1-3 mm 2 ). The shredded material was then subjected to collagenase/DNase digestion (20 ml solution per 1 g of material) and incubated over night at 37 C under constant shaking (300 r.p.m).…”

Integrative Analysis of Methylation and Gene Expression in Lung Adenocarcinoma and Squamous Cell Lung Carcinoma

“…In addition, we also identified several genes primarily associated with LUAD. According to Balabko et al (2014) RORC is a specific transcription factor in the tumor area of lung tissue in patients with LUAD. DLX5 (Kato et al, 2008;Balabko et al, 2014), MUC1 (Mashima et al, 2005;Molina-Pinelo et al, 2014), and KRT17 (Erdogan et al, 2009;Liu et al, 2018) were found to be overexpressed in LUAD.…”