Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death‐1/programmed cell death‐ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non‐small‐cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes’ signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti‐programmed cell death‐1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression‐free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8⁺ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor‐based immunotherapy.

In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin β1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin β1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin β1/PI3K/AKT and apoptosis induction.

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-β, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-β/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway.

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, the prognosis of patients with which is associated with both lncRNAs and cancer immunity. In this study, we collected gene expression data of 585 LUAD patients from The Cancer Genome Atlas (TCGA) database and 605 subjects from the Gene Expression Omnibus (GEO) database. LUAD patients were divided into high and low immune-cell-infiltrated groups according to the single sample gene set enrichment analysis (ssGSEA) algorithm to identify differentially expressed genes (DEGs). Based on the 49 immune-related DE lncRNAs, a four-lncRNA prognostic signature was constructed by applying least absolute shrinkage and selection operator (LASSO) regression, univariate Cox regression, and stepwise multivariate Cox regression in sequence. Kaplan–Meier curve, ROC analysis, and the testing GEO datasets verified the effectiveness of the signature in predicting overall survival (OS). Univariate Cox regression and multivariate Cox regression suggested that the signature was an independent prognostic factor. The correlation analysis revealed that the infiltration immune cell subtypes were related to these lncRNAs.

Radix Astragali (RA) herb with warm property and significant “tonifying qi” effects is indicated for the syndrome of internal cold due to Yang deficiency. The purpose of this research was to explore effects of Radix Astragali (RA) through PPAR signaling pathway on gene expression profiles related to energy metabolism in rats with the Yang‐deficiency cold (YDC) syndrome, for identifying the pathological mechanism of Yang‐deficiency cold (YDC) syndrome and the effects mechanism of RA. The results indicated that RA could significantly increase body weight (BM), cold and heat tendency (CT), overall temperature (OT), rectum temperature (RT), toe temperature (TT), energy intake (EI), and V(O₂)/V(CO₂) ratio (which indicates basal metabolism, BM) (P<0.05), enhancing the depressed metabolic function in YDC syndrome model rat. Our data also indicated differentially expressed genes (DEGs) related to energy metabolism involving lipids, carbohydrates, and amino acids metabolic process; the expression of CPT‐1 and FABP4 (ap2) was improved; PPAR, Glycolysis, Wnt, cAMP, MAPK, AMPK, and fatty acid degradation signaling pathway may be related to energy metabolism. However, the Chinese herbal medicine RA plays a certain role in promoting the metabolism of substances and energy in rats by its warming and beneficial effect. Our results suggest that the mechanism underlying the function of RA may take effect through the regulation of PPAR signaling pathway and related gene expression. Lipids, carbohydrates, and amino acids metabolic process may be affected to adjust the reduced metabolic function in the model animals. In general, results indicate that RA could promote energy metabolism in rats with the YDC syndrome via PPAR signaling pathway regulating the expression of CPT‐1 and FABP4 (ap2), which reflected the warm and qi tonifying properties of RA.