The tumor microenvironment is a dynamic cellular milieu that interacts with cancer cells and promotes tumor progression and metastasis. However, the specific mechanisms by which the tumor microenvironment impacts cancer cells’ behaviors remain poorly understood. In this study, enriched cancer-associated fibroblasts (CAFs) were observed in tumor tissues isolated from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) resistant non-small cell lung cancer (NSCLC) patients. CAFs isolated from tumor tissues were capable of producing tryptophan metabolite kynurenine (Kyn), which significantly increased the proliferation and EGFR TKIs resistance of NSCLC cells. In this study, it was further observed that the activation of tryptophan 2,3-dioxygenase (TDO) in CAFs, resulted in the enhanced capability of tryptophan metabolism in them compared to normal fibroblasts. As a result, Kyn produced by CAFs facilitated the up-regulation of Aryl Hydrocarbon Receptor (AhR) signals in NSCLC, thereby resulting in the downstream ATK and ERK signaling pathways activation. Finally, inhibition of AhR signals efficiently prevented tumor growth and development of EGFR TKIs resistance, eventually improved the outcome of EGFR TKIs, and described a promising therapeutic strategy for NSCLC.

Objectives The development and progression of malignancies are closely linked to hypercoagulability. As an early type of lung adenocarcinoma, ground glass nodules (GGNs) have been detected increasingly. Blood Maximum amplitude (MA) and mean platelet volume (MPV) are related to various conditions of hypercoagulability. Therefore, the role of MA and MPV in diagnosing lung adenocarcinoma cancer featured with GGNs was investigated in this case-control study. Methods The analyzed data of this study is derived from GGNs patients and healthy individuals in West China (Airport) Hospital Sichuan University. The differences between GGNs patients and healthy individuals were determined by one-way ANOVA, logistic regression or chi-squared test. The accuracy of diagnostic was performed by receiver operating characteristic curve (ROC). The relative mRNA expressions were studied by RT-qPCR. Results 470 patients diagnosed with GGNs which benign lesions (BN group) are inflammatory and malignant lesions (LC group) are adenocarcinoma in stage IA, and 235 healthy subjects (HC group) were enrolled in this study. Levels of MA and MPV were increased in LC group compared with BN and HC group ( p < 0.001, p < 0.001). When we combined MA and MPV, MA and MPV presented a sensitivity (SEN) of 0.809 and a specificity (SPE) of 0.774. And the area under the curve (AUC) increased to 0.871 (0.837–0.900) when confidence interval was 95%. Conclusion This study demonstrates that there have been systemic changes in coagulation disorders in the pathogenesis of GGNs. The diagnostic ability to different lung adenocarcinoma cancer featured with GGNs from benign or healthy controls can be improved by the combination of MA and MPV. Maximum amplitude and MPV may be used as biomarkers to detect lung adenocarcinoma cancer featured with GGNs.