Long-term chronic stress is an important factor in the poor prognosis of cancer patients. Chronic stress reduces the tissue infiltration of immune cells in the tumor microenvironment (TME) by continuously activating the adrenergic signaling, inhibits antitumor immune response and tumor cell apoptosis while also inducing epithelial-mesenchymal transition (EMT) and tumor angiogenesis, promoting tumor invasion and metastasis. This review first summarizes how adrenergic signaling activates intracellular signaling by binding different adrenergic receptor (AR) heterodimers. Then, we focused on reviewing adrenergic signaling to regulate multiple functions of immune cells, including cell differentiation, migration, and cytokine secretion. In addition, the article discusses the mechanisms by which adrenergic signaling exerts pro-tumorigenic effects by acting directly on the tumor itself. It also highlights the use of adrenergic receptor modulators in cancer therapy, with particular emphasis on their potential role in immunotherapy. Finally, the article reviews the beneficial effects of stress intervention measures on cancer treatment. We think that enhancing the body's antitumor response by adjusting adrenergic signaling can enhance the efficacy of cancer treatment.

Chronic obstructive pulmonary disease is a kind of chronic lung disease characterized by persistent air flow obstruction, which was the third leading cause of death in China. The incidence of COPD is steadily and increasing and has been a globally sever disease. Accordingly, it is urgently needed to explore how to diagnose and treat COPD timely. This study aims to find key genes to diagnose COPD as soon as possible to avoid COPD processing and analyze immune cell infiltration between COPD early stage and late stage. Two GEO datasets were merged as the merge data for analyses. 157 DEGs were used for GSEA analysis to find the pathway between COPD early stage and late stage. Above all, gene EXPH5 stood out from the screen as the most likely candidate diagnosis biomarker of COPD indicating the late-stage by least LASSO and SVM-RFE. ROC curves of EXPH5 were applied to represent the discriminatory ability through the area under the curve which is the gold standard to evaluate the accuracy of diagnosis and survival rate. The CIBERSORT algorithm was used to assess the distribution of tissue-infiltrating immune cells between two COPD stages. The diagnosis biomarker, gene EXPH5 had a positive correlation with NK cells resting; mast cell resting, eosinophils, and negative correlation with T cell gamma delta, macrophages M1, which underscore the role of gene and immune cell infiltration. To make results more reliable, we further analyzed the gene EXPH5 expression in single-cell transcriptome data and showed again that EXPH5 genes significantly downregulated in the late stage of COPD especially in the main lung cell types AT1 and AT2. In a word, our study identified genes EXPH5 as a marker gene, which adds to the knowledge for clinical diagnosis and pharmaceutical design of COPD.

Background SPATS2L (Spermatogenesis-associated serine-rich 2-like) is an intranuclear stress-response protein involved in chromosomal organization, ribosomal biogenesis, and translational control. Although there is mounting evidence that SPATS2L was involved in the carcinogenesis of some cancers, no thorough pan-cancer investigation of SPATS2L is available so far. Results Based on multiple databases, including TCGA, GTEx, CCLE, cBioPortal, TIMER2, ImmuCellAI, GDSC, and Reactome, we analyzed the expression, prognosis, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, drug sensitivity, and clinicopathological and prognostic relevance of SPATS2L in pan-cancer including 33 types of cancers. Lung adenocarcinoma (LUAD) specimens were enrolled to test the expression of SPATS2L by immunohistochemistry. LUAD cell A549 transfected with siRNA targeting SPATS2L was used in subsequent experiments. SPATS2L expression was dramatically increased in a variety of malignancies, while it was low in ACC, KICH, and LAML as indicated by multiple databases and confirmed by immunohistochemistry assays. Importantly, SPATS2L has been found to have prognostic and clinicopathological importance in several malignancies. SPATS2L expression was also linked to TMB and MSI in 9 types of cancers, and there was a link between SPATS2L expression and DNA methylation in 28 types of cancers. SPATS2L was also found to be highly linked with immune cell infiltration, ICP expression, stromal score, immune score, and ESTIMATE score in various malignancies, demonstrating their regulatory roles on the TME. Consistently, the results of GSEA and GSVA analyses revealed a substantial link between SPATS2L and certain cellular immunological responses. SPATS2L was found to be strongly linked to 173 anti-tumor drugs. The overexpressed SPATS2L in LUAD tissues was validated. Knockdown of SPATS2L inhibited LUAD cell proliferation and promoted apoptosis. Conclusions This study indicated that SPATS2L might be a potential cancer biomarker for the prognosis and immunotherapeutic response. SPATS2L expression in cancers may be involved in the regulation of the tumor immune microenvironment and drug sensitivity, which may be a new-targeted molecule for developing anti-tumor drugs and immunotherapy, especially for LUAD.