Lung cancer is the malignant tumor with the highest morbidity and mortality. The tumor-node-metastasis (TNM) staging has gradually shown its limitations in the accurate prediction of lung cancer, so it is urgent to construct a new clinical predictive model to guide the prevention and treatment of lung cancer. In recent years, as a comprehensive evaluation system based on peripheral immune related parameters, the value of peripheral immunoscore in the construction of predictive model has gradually become prominent. By quantifying the quantity and proportion of immune components in peripheral blood, the score can dynamically reflect the overall immune function and tumor microenvironment characteristics of the body. This paper systematically summarizes the latest research progress of peripheral immunoscore in early diagnosis, drug efficacy prediction, early warning of adverse reactions and prognosis evaluation of lung cancer, aiming to tap its potential clinical application value and provide some ideas and directions for developing new lung cancer-related predictive models.
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Humans ; Lung Neoplasms/drug therapy* ; Tumor Microenvironment ; Prognosis

Metastasis is a key cause of death in tumor patients, and a number of tumor patients have comorbid psychosomatic abnormalities and are in a state of chronic stress. Chronic stress affects the release of many kinds of hormones and neurotransmitters, such as epinephrine, norepinephrine, dopamine, glucocorticoids, cortisol, sex hormones, etc., through the hypothalamus–pituitary–adrenal axis and sympathetic nervous system. These substances can act on the β-adrenergic receptor, glucocorticoid receptor, etc., on tumor cells, immune cells, and other cells in the tumor microenvironment and promote the tumor progression and metastasis by directly enhancing the invasive and metastatic ability of tumor cells, inducing the formation of the immunosuppressive microenvironment and promoting tumor angiogenesis and other pathways. Antipsychotic drugs, β-blockers, and glucocorticoid receptor antagonists have inhibitory effects on chronic stress-mediated tumor metastasis and have achieved certain clinical efficacy. Relevant studies have been carried out on traditional Chinese medicine decoctions and monomers, which can inhibit tumor metastasis by modulating the immune microenvironment and reversing chronic stress-mediated hormonal changes. The psychological problems of tumor patients have gradually received attention, and the development of new anti-metastatic drugs based on the mechanism of action of chronic stress in promoting tumor progression and metastasis provides new ideas for the improvement of the overall efficiency of tumor prevention and treatment.

Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Objective To analyze and compare the disease burden, trends, and influencing factors of lung cancer in adolescents and young adults (AYAs) in China and globally from 1990 to 2021, providing a reference for the prevention and treatment of lung cancer in China. Methods Indicators of lung cancer disease burden in different genders and age groups in 204 countries or regions from 1990 to 2021 were retrieved and standardized from GBD 2021 database. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) of the standardized rates of lung cancer in AYAs in China and globally from 1990 to 2021; changes in incidence, mortality, and disability-adjusted life years (DALYs) rates due to population growth, aging, and epidemiological changes were analyzed; differences in lung cancer disease burden in AYAs in different socio-demographic index (SDI) regions were analyzed; and the influencing factors of lung cancer in AYAs in China and globally were explored. Results From 1990 to 2021, the age-standardized incidence rate (ASIR) (AAPC=−0.18%, P<0.001), age-standardized mortality rate (ASMR) (AAPC=−0.62%, P<0.001), and age-standardized DALYs rate (AAPC=−0.62%, P<0.001) of lung cancer in AYAs in China showed a downward trend, consistent with the global trend, but the decline in China was relatively small. During this period, the age-standardized rates of various indicators of lung cancer in males in China and globally were higher than those in females, and the burden of lung cancer in Chinese males was heavier. However, due to the significant downward trend in males, the gap in lung cancer burden between males and females was narrowing. At the same time, from 2013 to 2021, the ASIR [annual percent change (APC)=2.01%, P<0.001], ASMR (APC=1.46%, P<0.001), and standardized DALYs rate (APC=1.46%, P<0.001) in China showed an upward trend. From 1990 to 2021, among the main influencing factors for the incidence, mortality, and DALYs rates of lung cancer in Chinese AYAs, the contribution of aging was upward-pushing, while the increase in global indicators was mainly attributed to population growth. The global burden of lung cancer in AYAs was overly concentrated in high SDI regions. Although the gap in lung cancer burden between high SDI and low SDI regions was narrowing, it remained widespread. Globally, smoking, environmental PM2.5, insufficient fruit intake, second-hand smoke, and indoor air pollution were prominent risk factors. Conclusion From 1990 to 2021, the global and Chinese AYAs lung cancer incidence and mortality rates generally show a downward trend, but the female lung cancer burden relatively increases, especially in young women without a history of smoking. Continued efforts are needed to reduce the burden of lung cancer in AYAs, especially the specific risk for young women.

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

ObjectiveTo establish a qualitative analysis method for the chemical constituents of the reference sample of Xiao Xumingtang， and to establish the fingerprint of 15 batches of Xiao Xumingtang， so as to evaluate the quality consistency among batches. MethodAccording to the key information of Xiao Xumingtang in the Key Information Table of Ancient Famous Classical Formulas（25 Formulas）， the reference sample of this formula was prepared， and it was detected by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. The chemical components were identified by self-constructed database， consulting relevant literature， and comparing with the reference substances， and the components were assigned by comparing with single drug samples and negative samples lacking single drug. The fingerprint of the reference sample of Xiao Xumingtang was established using high performance liquid chromatography（HPLC）， and the common peaks were assigned and identified through single drug samples and negative samples lacking single drug. ResultBased on the information of MS fragments， relevant literature， and database retrieval， a total of 64 compounds were identified and inferred from the reference sample of Xiao Xumingtang， including 31 flavonoids， 8 terpenoids， 12 triterpenoid saponins， 2 phthalides， 3 phenylpropanoids， 2 gingerols， 5 alkaloids， and 1 cyanoside. Among them， 21 were derived from Scutellariae Radix， 10 from stir-fried Glycyrrhizae Radix et Rhizoma， 9 from Ginseng Radix et Rhizoma， 8 from Paeoniae Radix Alba， 4 from Saposhnikoviae Radix， 3 from Stephaniae Tetrandrae Radix， 3 from Chuanxiong Rhizoma， 2 from Aconiti Lateralis Radix Praeparata， 2 from Zingiberis Rhizoma Recens， 1 from Ephedrae Herba， and 1 from Armeniacae Semen Amarum. The established HPLC fingerprint of the reference sample of Xiao Xumingtang had 23 common peaks， among which， peaks 1 and 2 were derived from Paeoniae Radix Alba， peaks 3 and 7 from Saposhnikoviae Radix， peaks 4， 8 and 9 from Stephaniae Tetrandrae Radix， peaks 10， 17， 18， 20 and 21 from stir-fried Glycyrrhizae Radix et Rhizoma， peaks 11-16， 19 and 22 from Scutellariae Radix， peak 5 from Chuanxiong Rhizoma， peak 23 from Zingiberis Rhizoma Recens， peak 6 was the common component of stir-fried Glycyrrhizae Radix et Rhizoma and Scutellariae Radix. A total of 10 compounds including albiflorin（peak 1）， paeoniflorin（peak 2）， cimicifugoside（peak 3）， 5-O-methylvisammioside（peak 7）， baicalin（peak 11）， sec-O-glucosylhamaudol（peak 13）， oroxylin A-7-O-β-D-glucuronide（peak 15）， wogonoside（peak 16）， glycyrrhizic acid（peak 21） and 6-gingerol（peak 23） were identified. The similarities of 15 batches of reference samples were>0.999， indicating that the reference samples had good consistency. ConclusionThrough the identification of the chemical constituents in the reference sample of Xiao Xumingtang， it is clear that the composition of the samples is mainly composed of flavonoids and triterpenoid saponins. The established fingerprint can basically reflect the overall chemical characteristics of the reference sample of Xiao Xumingtang， which can provide a basis for the quality research of its compound preparations.

Based on the concepts of "people-oriented" in traditional Chinese medicine and "tumor-suppression" in modern medicine， we have combed the studies on the spatial and temporal evolution of tumor metastasis and its biological characteristics in different perspectives， and initially proposed the theory of tumor metastasis from the perspective of the dynamic game between the tumor cells and the body's immune system under the theory of the integration of Chinese and Western medicine， that is， the formation of metastasis is the result of the dynamic evolution of the cancer cells and their surrounding environmental factors in the body over time and space. It is believed that the symptomatic manifestation of metastasis is systematic， the triggering factors of metastasis are constant， and the clinical outcome of metastasis is staged. Accordingly， it is proposed to understand the mechanism of metastasis from the perspective of spatial and temporal dynamics， to establish a clinical and pathological model for identifying metastasis， and to reveal the critical point of metastasis， so as to facilitate the change of the research on tumor metastasis from static to dynamic， and provide ideas for the formulation of metastasis prevention and treatment strategies， and the construction of a new system of metastasis prevention and treatment in the clinical tumor field.

Immunotherapy has become a global focus in cancer clinical practice and scientific research. In the past two years, PD-1\PD-L1 and CTLA-4 inhibitors, especially Nivolumab, Pembrolizumab, Atezolizumab and Lpilimumab, have been used in non-small cell lung cancer, colon cancer. Promising results have been obtained in malignancies such as melanoma and urinary tract cancer. Traditional Chinese medicine has a long history in China. Modulating immune checkpoints has certain advantages in treating malignant tumors, and it has shown good efficacy in improving its adverse events. This article reviews the role of traditional Chinese medicine in regulating immune checkpoints and improving adverse reactions and its application prospects in immunomodulatory treatment.

Lung cancer is the malignant tumor with the highest incidence and lethality globally.In recent years,emerging immunotherapy based on the immune checkpoint inhibitors,programmed cell death protein-1 and its ligand(PD-1/L1),as a representative,has made revolu-tionary breakthroughs in the field of lung cancer.The indications for this treatment mode have moved from driver-gene-negative advanced or locally advanced lung cancer to adjuvant and neoadjuvant treatment of perioperative lung cancer,and an increasing number of mono-clonal antibodies against PD-1 and PD-L1 has been approved for the treatment of lung cancer.However,with the widespread use of immun-otherapy,the problem of drug resistance has gradually come to the fore.Only a small proportion of the overall lung cancer population re-sponds to immunotherapy,bringing a new round of challenges to lung cancer treatment.In this paper,the clinical status of immunotherapy resistance in lung caner is reviewed,and cutting-edge advances in knowledge of resistance mechanisms and coping strategies are reviewed,with the aim of providing clinicians with ideas and the basis for formulating individualized,precise treatment plans.

The immune microenvironment plays a key role in the development and progression of tumors.In recent years,with the rapid advancement of high-throughput sequencing technologies,researchers have gained a deeper under-standing of the composition and function of immune cells in the tumor microenvironment.However,traditional bulk sequenc-ing technologies are limited in resolving heterogeneity at the single-cell level,constraining a comprehensive understanding of the complexity of the tumor microenvironment.The advent of single-cell RNA sequencing technology has brought new opportunities to uncover the heterogeneity of the immune microenvironment in lung cancer.Currently,T-cell-centered im-munotherapy in clinical settings is prone to side effects affecting prognosis,such as immunogenic drug resistance or immune-related pneumonia,with the key factor being changes in the interactions between immune cells and tumor cells in the tumor microenvironment.Single-cell RNA sequencing technology can reveal the origins and functions of different subgroups within the tumor microenvironment from perspectives such as intercellular interactions and pseudotime analysis,thereby discovering new cell subgroups or novel biomarkers,providing new avenues for uncovering resistance to immunotherapy and monitoring therapeutic efficacy.This review comprehensively discusses the newest research techniques and advancements in single-cell RNA sequencing technology for unveiling the heterogeneity of the tumor micro environment after lung cancer immunotherapy,offering insights for enhancing the precision and personalization of immunotherapy.