Portal vein tumor thrombus (PVTT) is among the most lethal complications of hepatocellular carcinoma (HCC), yet its molecular mechanisms and immune features remain poorly characterized. To address this gap, we performed a comprehensive multi-omics analysis of 99 specimens from 47 patients, integrating nCounter profiling, single-cell RNA sequencing, digital spatial profiling, and proteomics to construct the first spatial map of the PVTT microenvironment. These analyses revealed marked intratumoral heterogeneity and enrichment of myofibroblast-like cancer-associated fibroblasts (myCAFs) arising through a macrophage-to-myofibroblast transition. Nidogen-1 (NID1) was identified as a stromal driver of immune barriers, highly expressed in PVTT cores and associated with impaired antitumor immunity. Guided by these mechanistic insights, we repurposed acarbose, a Food and Drug Administration-approved drug, to inhibit the NID1 axis. Functional assays demonstrated that acarbose disrupted myCAF-mediated immune barriers, suppressed PVTT progression, and synergized with anti-programmed death-1 (anti-PD-1) therapy in preclinical models. Furthermore, analysis of an independent clinical cohort of 810 HCC patients revealed a substantially lower incidence of PVTT among those receiving acarbose, underscoring its translational potential. Collectively, these findings establish the immune-stromal landscape of PVTT, uncover NID1-driven stromal remodeling as a mechanism of immune evasion, and highlight drug repurposing as an immediately actionable strategy to improve outcomes in HCC with PVTT.

BACKGROUND:Androgenic alopecia (AGA) represents the most predominant form of hair loss in clinical practice, yet currently approved pharmacological options (e.g., finasteride and minoxidil) face limitations in safety and long-term efficacy. Shen-Ying-Yang-Zhen formula (SYF) is a classical prescription in traditional Chinese medicine to AGA; nevertheless, its specific mechanisms of action in addressing AGA remain to be further explored and elucidated. In our study, we for the first time propose that SYF uniquely reshapes the perifollicular microenvironment through dual regulation of oxidative stress and angiogenesis, thus providing a potential medication for AGA. METHODS:In this study, the chemical constituents of SYF were identified using UPLC-MS. An AGA mouse model was established by induction with testosterone propionate (TP), and a human dermal papilla cell (HDPC) model was induced by dihydrotestosterone (DHT). The mechanism underlying SYF treatment for AGA was examined by merging network pharmacology with RNA sequencing, and the findings were corroborated through flow cytometry, multiple immunofluorescences, Western blotting, RT-qPCR, and ELISA techniques. RESULTS:In the AGA mouse model, histological analysis revealed that oral administration of SYF significantly increased skin thickness and hair follicle density (2.8-fold vs. TP group, p < 0.001). Immunofluorescence staining further confirmed that SYF treatment promoted a 2.9-fold increase in p-S6-positive hair follicles-indicative of anagen-phase induction (p < 0.001). Network pharmacology and RNA-seq analyses showed that SYF treatment was associated with cellular oxidative stress and the angiogenic microenvironment around AGA hair follicles, which may be related to targets such as VEGF and Akt Additionally, expression of Ki67, SRY-box transcription factor 9, phospho-S6 ribosomal protein (p-S6), and Nrf2 was enhanced in the skin of the SYF-treated mice, whereas reactive oxygen species expression was decreased. RT-qPCR analysis revealed downregulation of follicle degradation-related factors DKK1, IL-6, and TGFβ1, along with decreased Caspase-9 expression and upregulated key targets VEGF and Akt in the VEGF/Akt/Caspase-9 signaling axis. In the DHT-HDPC model, SYF promoted the proliferation of HDPCs and elevated the Bcl-2/Bax ratio, which in turn suppressed apoptosis of HDPCs in vitro. CONCLUSION:SYF shows promise as a therapeutic agent for prevention of hair loss by improving oxidative stress and angiogenesis in the area surrounding hair follicles in AGA. It reduces apoptosis in DHT-treated HDPCs by regulating the VEGF/Akt/Caspase-9 signaling axis. This multi-target, systems-level approach highlights SYF's potential as a novel therapeutic agent for AGA.

ETHNOPHARMACOLOGICAL RELEVANCE:Wu-wei-zi decoction (WWZ) is a clinically utilized classical herbal formula for non-small cell lung cancer (NSCLC). Nevertheless, the underlying mechanism of WWZ-treated lung cancer that is still unknown requires further investigation. AIM OF THE STUDY:This study investigates how WWZ reprograms tumor immune micro-environment (TIME) by regulating myeloid-derived suppressor cells (MDSCs). METHODS:Orthotopic NSCLC models were established in immunocompetent and immunodeficient mice to evaluate WWZ efficacy. MDSCs dynamics (frequency, apoptosis, immunosuppressive function) and CD8+ T cells infiltration were assessed by flow cytometry. Target specificity was validated by depleting MDSCs with anti-Gr-1 antibodies. The key pathways were identified via network pharmacology, molecular docking and RNA-sequencing, validated through immunofluorescence co-localization in human NSCLC tissues, bioinformatic analysis, and CD73-knockdown in the immortalized MDSCs (MSC-2). RESULTS:WWZ significantly prolonged survival by decreasing MDSCs infiltration and immunosuppressive function to restore the CD8+ T cells cytotoxicity. MDSCs depletion abrogated WWZ's therapeutic effects, confirming their pivotal role. Mechanistically, we reveal for the first time that IL-6 modulates MDSCs immunosuppression via CD73 activation in NSCLC. WWZ suppressed the IL-6/CD73 axis in MDSCs, decreasing CD73+ MDSCs and downregulating immunosuppressive markers iNOS/Arg1, thereby reversing TIME suppression. CONCLUSIONS:WWZ modulates immunosuppressive activity by inhibiting the IL-6/CD73 axis in MDSCs in the TIME, thereby delaying tumor progression in NSCLC. This study provides the first mechanistic evidence supporting WWZ's clinical utility as a TCM immunomodulatory agent for NSCLC.

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease that affects the quality of life and mental health of approximately 150 million people worldwide. Ze-Qi-Tang (ZQT) is a classic compound used in China for lung disease; however, its mechanism of action in psoriasis remains unclear. This study aimed to investigate the therapeutic effect of the ZQT formula on psoriasis and explore the underlying molecular mechanisms.MethodsPeripheral blood samples were collected from patients with psoriasis and healthy individuals. Flow cytometry was used to detect changes in the proportions of myeloid-derived suppressor cells (MDSCs) and other immune cells. Psoriasis was induced in mice by the daily application of imiquimod. ZQT was administered separately or in combination with anti-Gr1 antibody to deplete MDSC. The glycolysis levels of the MDSCs were detected using a Seahorse analyzer. The p21/Hif1α/Glut1 pathway was identified and validated by mRNA sequence, RT-qPCR, WB, IF, and the application of p21 inhibitor UC2288.ResultsThe number of MDSCs was significantly increased in patients with psoriasis, with the increased expression of p21, Hif1α, and Glut1 in MDSCs. ZQT significantly alleviated psoriasis-like skin lesions in mice. ZQT formula significantly reduced the number of MDSCs in psoriatic-like mice and enhanced their suppressive capacity for T cells. The efficacy of ZQT in alleviating psoriatic dermatitis is compromised by MDSC depletion. ZQT decreased the expressions of p21, Hif1α, and Glut1-induced glycolysis in MDSCs, thereby inhibiting Th17 cell differentiation.ConclusionThese suggest that ZQT alleviates IMQ-induced psoriatic dermatitis, by inhibiting p21/Hif1α/Glut1-induced glycolysis in MDSCs.

Background Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods.Methods To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation-qPCR (MeRIP-qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis.Results Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes.Conclusion In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.

Ethnopharmacological relevance: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. Aim of the study: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). Materials and methods: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1 beta/TD + IL-1 beta in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1 beta-mediated apoptosis of G-MDSCs. Results: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1 beta-mediated NF-kappa B signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8(+) T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. Conclusion: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1 beta-mediated NF-kappa B signalling pathway, reshaping the tumour

This paper explored the theory of “Ying Wei Sheng Hui” from the perspective of blood circulation in modern medicine. Ying qi and Wei qi keep running all the time in the body and play the role of defending, warming, regulating and nourishing, etc. It is quite similar to modern medicine’s blood circulation that runs round and forth in the human body, exerting functions such as material transport, body fluid regulation, maintaining homeostasis, achieving blood defense and endocrine secretion. There is a certain internal relationship between “Ying Wei Sheng Hui” and human blood circulation, but the meaning of “Ying Wei Sheng Hui” is much more than blood circulation.

本文以5 部《黄帝内经》英译本及5 部国内外中医术语英译标准为语料,对《黄帝内经》中29 条隐喻类疾病名英译现状进行分析,发现存在翻译策略不一致、一词多译、信息还原度不足等现象.提出隐喻类疾病名英译应在准确理解疾病内涵的基础上,以"信息传递完整"为翻译原则;同时根据疾病命名特点,将 29 条隐喻类疾病名分为"完全隐喻命名"和"部分隐喻命名"两大类,并根据具体情况提出5 种翻译策略,即"直译""直译(西医对应词)""直译+增译""直译+音译""意译".

Background: Psoriasis is a chronic and incurable skin disorder that causes inflammation. There is an urgent clinical need for new treatments. We identified the natural compound indirubin as a potential potent agent for the treatment of psoriasis, but it's therapeutic effect and underlying mechanisms were not well understood.Methods: Peripheral blood and skin tissues from psoriasis patients and healthy individuals were collected. Bio-informatics analysis was performed to investigate LAT1 expression and associated signal pathways in psoriasis skin lesions. A mouse model of psoriasis was established. Indirubin was administered separately or in combi-nation with MDSCs depletion or adoptively transferred MDSCs. JPH203, rapamycin, siRNA, and NV5138 were further used to investigate the potential mechanism by which indirubin regulates MDSCs.Results: Psoriasis patients had increased numbers of MDSCs in their blood and skin lesions, with high expression of Lat1. The upregulation of LAT1 expression and the arginine synthesis pathway was observed in psoriasis skin lesions. The number of MDSCs was increased, while their inhibitory effect on psoriatic T cells was decreased. Indirubin decreased Lat1 expression on the surface of MDSCs, inhibited mTOR pathway activation, upregulated Arg1 expression in MDSCs, and enhanced the immunosuppressive activity of MDSCs while inhibiting CD4+CCR6+ T cells.Conclusion: This study demonstrates indirubin's pharmacological and therapeutic effects, providing a basis for future clinical application in treating psoriasis.

目的:基于"肺主皮毛"理论探究银屑病与肺癌共病的内在免疫机制.方法:C57BL/6J小鼠64只,随机分为肺癌组、共病1组、肺癌-甲氨蝶呤组、共病1-甲氨蝶呤组、银屑病组、共病2组、肺癌-顺铂组、共病2-顺铂组,每组8只,分别根据前期研究给予肺癌和银屑病造模,甲氨蝶呤组给予200 μL甲氨蝶呤1 mg/kg灌胃治疗,顺铂组给予2 mL/kg顺铂100 μL腹腔注射,每日1次,连续7d.观察银屑病皮肤红斑和鳞屑及病理学变化,活体成像检测肺癌小鼠肺部荧光信号,流式细胞术检测免疫细胞数量.结果:与肺癌组比较,共病1组小鼠肺部荧光信号显著增强(P＜0.01),CD3+T细胞、MDSCs数量显著增加(P＜0.01),CD4+T、CD8+T细胞数量显著减少(P＜0.01);与银屑病组比较,共病2组皮损无显著改变,CD3T细胞、CD4+T细胞显著减少(P＜0.01),MDSCs数量显著增加(P＜0.01);顺铂改善共病2组小鼠脾肿大,增加CCR64T细胞数量(P＜0.01),减少MDSCs数量(P＜0.01);甲氨蝶呤显著改善小鼠脾肿大,并增加CD8+T细胞数量(P＜0.01).结论:银屑病显著促进共病模型肺癌进展,肺癌削弱了银屑病的治疗,顺铂和甲氨蝶呤干预在一定程度上缓解了共病模型进展.

中医药是中国文化的精髓,是打开中华文明宝库的钥匙,而中医药术语则是打开中医药宝库的钥匙,有助于准确把握和深刻理解中医药所蕴涵医学、哲学的文化特征和内涵.中医药学是与西方医学不同的医学体系,中医药术语具备哲学性、文化性和专业性等多重属性,准确地翻译好这些既具独特文化内涵又自成体系的中医药术语,是中医药对外传播的关键.对中医药术语英译的趋势、问题进行分析和总结,有利于对外讲述"中医"故事时,准确传达中医药丰富的哲学文化以及医学内涵,增强中国文化的吸引力,树立文化自信.因此,笔者分析近30年来国内外中医药术语英译的趋势和问题,探讨如何进一步推进中医药术语英译研究,并对未来提出展望.

The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer.However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear.After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells.Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc).Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer.In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect.Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future.

在中医药悠久的发展历程中,语言的字、词含义也在不断丰富扩充,为避免词汇系统庞杂,一词多义成为普遍现象.《黄帝内经》是我国现存成书最早的医学经典,其文言简意深,存在较多一词多义现象,也是造成其翻译困难的主要因素之一.《黄帝内经》作为中医学代表性著作,其准确恰当的译文对中医药国际化传播大有裨益.目前,对于《黄帝内经》一词多义翻译的相关研究多集中在对某一字词如何翻译的讨论,较少对这一现象的英译策略进行研究.本文以《黄帝内经》中"经"字为例,以李照国、文树德、吴连胜全译本为基础,对比分析"经"字各义项译文,进而探讨《黄帝内经》一词多义现象英译策略.

从古代文献入手,整理分析味觉障碍的病因病机,并结合新型冠状病毒肺炎味觉障碍特征,认为新型冠状病毒肺炎味觉障碍病因病机与脾胃、膜原关系密切,且以湿浊内阻为病机关键.挖掘古代文献中味觉障碍的治法、方药,认为新型冠状病毒肺炎味觉障碍的治疗当以祛湿化浊为机要,可以根据不同证候,分别施用白术厚朴汤、甘露饮加广藿香、苓术饮、清透遏膜方、口淡方5方,或与新型冠状病毒肺炎主治方配合使用,另可使用针灸治疗.

髓源抑制细胞(MDSC)是来源于骨髓的一群具有免疫抑制作用的异质性细胞群体,在病理状态下扩增,发挥调节机体自身免疫的作用.MDSC的早期研究聚焦于其在肿瘤微环境中的免疫抑制活性方面,近年逐渐有研究者将视角拓展至其在自身免疫性疾病、器官移植、妊娠和炎症等非肿瘤领域的作用.在非肿瘤疾病中,MDSC在一定程度上发挥正向调节作用,其通过调节T细胞、B细胞、NK细胞等免疫细胞,抑制过激的免疫反应,进而影响疾病的发展.加强MDSC在非肿瘤疾病中作用的研究,才能更加全面地认识MDSC,从而更好地阐明MDSC在不同疾病中的作用.

Background and purposeNeuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17–CD4+ T lymphocyte–β-endorphin axis.MethodsAfter receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4+ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and β-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested.ResultsThe pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL-17A in CD4+ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted.ConclusionWe, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17–CD4+ T lymphocyte–β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.

BACKGROUND:Beekeeping and honey gathering are traditional forms of agricultural farming in China. However, only few studies have focused on the nutritional status and health level of this special occupational group.OBJECTIVE:By comparing the health status of apiculturists (beekeepers) and vegetable farmers in plain areas of Hubei Province, and analyzing the influence of dietary structure and intake on their nutritional level, this paper provides a scientific theoretical basis for the further development of health education and disease prevention for beekeepers.METHODS:From February to April 2016, 191/236 beekeepers (80.9% of the total beekeepers) with large-scale breeding (300-500 colonies) and 182 vegetable farmers in the same area were sampled by the cluster sampling method. Their nutrient composition was analyzed using a human body composition analyzer, dietary structure information was collected using the dietary frequency query method, and cognitive function was investigated. In addition, blood samples of both groups were collected.RESULTS:A total of 362 valid questionnaires (beekeepers/vegetable farmers: 185/177) were collected, with an effective response rate of 97.1% (362/373). Both beekeepers and vegetable farmers were overweight, and the beekeepers' grip strength was much stronger than that of the vegetable farmers' regardless of gender. The dietary structure of beekeepers is very unique: 29.7% (55/185) of beekeepers indicated consuming royal jelly regularly for more than 10 years. Their main foods are grain, cereals, and fresh vegetables; 68.1% (126/185) of the beekeepers never drank milk and other dairy products, and their overall nutrient intake is unbalanced. The average intake of cellulose in this group was also significantly higher than that in the epidemiological survey in the same sex and age group. The intake of vitamin A and selenium in the beekeepers group was significantly higher than that in the vegetable-farmers group (all P<.001). The blood indices of creatinine (P=.03) and blood copper (P<.001) in the beekeepers group were significantly higher than those in the vegetable-farmers group, and the total protein, albumin, calcium, sodium, potassium, phosphorus, folic acid, and vitamin B12 in the beekeepers group were significantly lower than those in the vegetable-farmers group (P<.03 for potassium and P<.001 for others). The total Mini-Mental State Examination (MMSE) score of the beekeepers group was 28.1, significantly higher (P=.006) than that of the vegetable-farmers group (23.3).CONCLUSIONS:The beekeepers in this area have their special dietary structure, body nutrient level, and disease characteristics. The cognitive level of the beekeepers who regularly consume royal jelly is significantly higher than that of their peers. The chronic diseases of this special occupational group are closely related to their lifestyle and nutritional status, so more attention and in-depth studies are needed to improve the quality of life of this population.

肿瘤微环境(TME)在肿瘤发生发展中发挥重要促进作用.广泛存在于TME中的髓源抑制细胞(MDSCs)是介导肿瘤免疫逃逸的主要效应细胞群.单核细胞样髓源抑制细胞(M-MDSCs)作为MDSCs中除中性粒细胞样髓源抑制细胞(PMN-MDSCs)以外的另一主要亚型,因其具备PMN-MDSCs不具备的广谱免疫抑制活性和高度可塑性,即M-MDSCs在癌症初期被招募至肿瘤部位,对T细胞、NK细胞等发挥直接免疫抑制作用,另可分化为肿瘤相关巨噬细胞(TAM)、炎症性树突状细胞(Inf-DCs)和PMN-MDSCs,从而增加肿瘤治疗难度,故研究者逐渐把目光由数量上占主导的PMN-MDSCs转向占比较少的M-MDSCs.根据M-MDSCs在TME中募集迅速、分化多样和功能复杂的特点,以其为靶点的免疫疗法可从耗竭数量、干预分化和抑制功能3方面入手,以期增强临床抗肿瘤疗效.虽然国内外PMN-MDSCs研究颇丰,但聚焦于M-MDSCs的中文综述鲜有报道,本文拟从TME中M-MDSCs特点出发,首次对M-MDSCs免疫抑制作用及其靶向治疗进行综述.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.