Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity

Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.

Single nucleus/cell RNA-seq of the chicken hypothalamicpituitaryovarian axis offers new insights into the molecular regulatory mechanisms of ovarian development

The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined.This study provides the first comprehensive,unbiased,cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens.Within the hypothalamus,pituitary,and ovary,seven,12,and 13 distinct cell types were identified,respectively.Results indicated that the pituitary adenylate cyclase activating polypeptide(PACAP),follicle-stimulating hormone(FSH),and prolactin(PRL)signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone(GnRH),FSH,and luteinizing hormone(LH)within the hypothalamus and pituitary.In the ovary,interactions between granulosa cells and oocytes involved the KIT,CD99,LIFR,FN1,and ANGPTL signaling pathways,which collectively regulate follicular maturation.The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis.Additionally,gene expression analysis revealed that relaxin 3(RLN3),gastrin-releasing peptide(GRP),and cocaine-and amphetamine regulated transcripts(CART,also known as CARTPT)may function as novel endocrine hormones,influencing the HPO axis through autocrine,paracrine,and endocrine pathways.Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP,RLN3,CARTPT,LHCGR,FSHR,and GRPR in the ovaries of Lohmann layers,potentially contributing to their superior reproductive performance.In conclusion,this study provides a detailed molecular characterization of the HPO axis,offering novel insights into the regulatory mechanisms underlying reproductive biology.

Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

Dynamic interplay between adhesion surfaces in carcinomas:Cell-cell and cell-matrix crosstalk

Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology.

Crosstalk between mesenchymal stem cell and cardiomyocytes prevents pathological myocardial hypertrophy

Aim The present study aims to investigate whether BMSCs transplantation may inhibit hypertrophic hearts and its underlying mechanisms. Background There is no evidence so far that Bone marrow-derived mesenchy- mal stem cells （BMSCs） can heal pathological myocardial hypertrophy. Methods To observe the antihypertrophic actions, BMSCs was indirectly cocultured with NRVCs in vitro, or intramyocardially transplanted into hypertrophic hearts in vivo. Results ISO-induced typical hypertrophic characteristics of cardiomyocytes were obviously preven- ted by BMSCs in the co-culture model in vitro and after BMSCs transplantation in vivo. Furthermore, the activation of the Ca2＋/calcineurin/NFATc3 hypertrophic pathway was shown abrogated in the presence of BMSCs both in vitro and in vivo. Interestingly, blockage of VEGF release from BMSCs but not bFGF and IGF-1 can abolish the protec- tive effects of BMSCs on cardiomyocytes hypertrophy. Consistently, VEGF administration attenuated ISO-induced BNP and β-MHC expression and the activation of Ca2＋/cal- the enlargement of cellular size, the augment of ANP, cineurin/NFATc3 hypertrophic pathway, and these can be abrogated by blocking VEGFR-1, indicating VEGFR-1 is involved in the antihypertrophic role of VEGF. We further find that the ample VEGF secretion contributing to the anti-hypertrophic effects of BMSCs originates from BMSCs interplay with cardiac cells but not BMSCs or cardiomyo- cytes alone. Conclusions Thus, mesenchymal stem cells are able to inhibit myocardial hypertrophy via interacting with cardiomyocytes so as to promote VEGF release which inhibits the activation of the Ca2＋/calcineurin/NFATc3 hypertrophic signaling pathway in cardiac cells, in addition to its well-recognized ability to ameliorate myocardial injuries by replacing dead cells.

The crosstalk between endothelial cells and vascular smooth muscle cells during low shear stress:a proteomic-based approach

Instruction Shear stress,caused by the parallel frictional drag force of blood flow,is a biomechanical force which plays an important role in the control of blood vessels growth and functions [1]. Clinical researches had found out that atherosclerotic le-

周细胞-内皮细胞Crosstalk在心肌缺血后微血管新生中的研究进展

心血管疾病是世界公共卫生问题,是人类主要的死亡原因之一。治疗性血管新生能够有效减轻心肌缺血损伤并改善心功能,已成为心肌缺血后重要的补充治疗策略。周细胞-内皮细胞Crosstalk对心肌缺血后微血管新生的调控机制主要包括周细胞通过血管基底膜直接接触内皮细胞和旁分泌调节两种模式。其中,旁分泌调节主要通过促血管新生细胞因子和激活多种信号通路,以促进微血管新生和成熟,对稳定血管/血液系统及改善心脏功能等具有重要作用,因此,周细胞-内皮细胞Crosstalk是心肌缺血后微血管新生的关键环节。本文综述了周细胞-内皮细胞Crosstalk在心肌缺血后微血管新生中的机制及作用,以期为心肌缺血的补充治疗方案提供思路。

程序性细胞死亡在脑卒中后认知障碍中的研究进展

脑卒中后认知障碍(post-stroke cognitive impairment,PSCI)是脑卒中后常见并发症之一,对卒中患者的生活质量影响较大,但发病机制尚未能完全解释清楚。越来越多的证据表明,程序性细胞死亡(programmed cell death,PCD)机制与PSCI有关,包括细胞凋亡、坏死性凋亡、细胞焦亡、泛凋亡、PARP-1依赖性细胞死亡和铁死亡等。因此,清楚了解各种PCD机制及其与PSCI的关系,阐明PCD在疾病发病机制中的作用至关重要。文章综述了与PSCI相关的6种PCD途径,总结其在PSCI中的作用机制,并阐述了不同途径之间可能存在的串扰,以期为临床靶向PCD途径的调节因子来治疗PSCI提供资料依据。

骨免疫学视角下绝经后骨质疏松症防治新靶点:MΦ-BMSCs串扰

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是以骨量下降、骨结构破坏、易发生骨折为特征的代谢性骨病。PMOP已严重威胁女性健康,制约社会经济发展。近年来雌激素缺乏引起PMOP相关机制研究取得进展,但仍未得到充分阐明。骨免疫学研究显示PMOP病理过程伴随着慢性炎症和免疫系统的参与。巨噬细胞(macrophage,MΦ)是重要的免疫细胞,被报道在骨稳态和再生中发挥作用。巨噬细胞的耗竭能加重OVX小鼠的骨丢失,减少骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)数量,降低BMSCs成骨分化能力。巨噬细胞的缺失对骨形成的影响似乎超过了其对破骨细胞活性的影响,MΦ与BMSCs之间的串扰可能在这一环节发挥着重要作用。本文基于骨免疫学理论对MΦ-BMSCs串扰和PMOP的相关性进行综述,旨在为PMOP的防治研究提供新思路。

消退素D1对结肠癌细胞K-Ras/Notch信号通路串话的影响

目的 探讨消退素D1(Rv D1)对SW620结肠癌细胞K-Ras/Notch信号通路串话的影响及作用机制。方法 采用CCK-8和克隆形成方法评估Rv D1(0.0、62.5、125.0、250.0、500 nmol/L)对SW620结肠癌细胞短期和长期增殖的影响;将SW620结肠癌细胞分成空白组、Rv D1组、K-Ras组、K-Ras+Rv D1组。空白组不进行处理,K-Ras组和K-Ras+Rv D1组转染K-Ras质粒,Rv D1组和K-Ras+Rv D1组用250 nmol/L的Rv D1处理。蛋白质印迹法检测IL-6、K-Ras、NICD、p-p65、p65、vimentin、N-cadherin和E-cadherin蛋白表达;免疫荧光法检测IL-6、K-Ras和NICD蛋白表达;Transwell实验检测细胞侵袭和迁移水平。结果 125.0、250.0、500.0 nmol/L Rv D1抑制SW620细胞增殖和克隆形成能力(P<0.05)。在Rv D1组中,IL-6、K-Ras、NICD、p-p65、vimentin、N-cadherin蛋白表达均低于空白组,E-cadherin表达高于空白组,差异有统计学意义(P<0.05);K-Ras组的NICD、p-p65、vimentin、N-cadherin的蛋白表达高于空白组,E-cadherin表达低于空白组,差异有统计学意义(P<0.05);K-Ras+Rv D1组的NICD、p-p65、vimentin、N-cadherin表达及细胞侵袭和迁移水平均低于K-Ras组,E-cadherin表达高于K-Ras组,差异有统计学意义(P<0.05)。结论 Rv D1通过抑制IL-6表达,抑制K-Ras对Notch信号通路串话,降低下游核因子-κB水平和上皮-间质转化特性,削弱结肠癌细胞的侵袭转移能力。

调节性细胞死亡在血管性痴呆中的作用及中医药调控机制概述

血管性痴呆(vascular dementia,VD)是一种由大脑损伤所引起的神经退行性疾病,其发病机制尚未完全明确。现有大量研究表明,凋亡、焦亡、自噬、铁死亡以及铜死亡等调节性细胞死亡(regulated all death,RCD)的发生机制与VD病理机制有关。因此,明确这些细胞死亡发生机制与VD病理机制之间的联系,阐述RCD在疾病发病机制中的作用,对于VD的防治具有重要意义。本文就5种RCD的发生机制在VD中的作用展开综述,并总结了近几年中药通过干预这几种RCD防治VD的研究进展,以期为进一步挖掘治疗VD的潜在靶点及中药新药的开发提供参考。

心肌缺血再灌注损伤中的线粒体相关细胞器串扰

细胞器损伤是导致心肌缺血再灌注损伤的重要因素。这种损伤会导致线粒体及相关细胞器的功能改变。线粒体与其他细胞器的串扰同样影响心脏缺血再灌注损伤的发生发展,例如线粒体相关内质网膜使得线粒体和内质网“无缝连接”,调节线粒体和内质网之间的细胞器和代谢物(包括离子、脂质和蛋白质)交换,从而影响心肌缺血再灌注损伤。然而,线粒体与相关细胞器串扰是触发心肌缺血再灌注损伤的关键因素,目前相关报道有限。因此,该文阐述了线粒体与内质网、溶酶体和细胞核串扰在心肌缺血再灌注损伤中的作用,旨在为靶向线粒体与其他细胞器的串扰治疗心肌缺血再灌注损伤的研究提供一定的理论依据。

Crosstalk network among multiple inflammatory mediators in liver fibrosis

Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells,cytokines,and the related signaling pathways.Damaged hepatocytes induce an increase in proinflammatory factors,thereby inducing the development of inflammation.In addition,it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis.The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production,which in turn initiate the fibrotic response.Compared with the past,the research on the pathogenesis of liver fibrosis has been greatly developed.However,the liver fibrosis mechanism is complex and many pathways involved need to be further studied.This review mainly focuses on the crosstalk regulatory network among inflammatory cells,cytokines,and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases.Moreover,we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.

Pancreatic cancer stem cell markers and exosomes-the incentive push

Pancreatic cancer(Pa Ca) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells(CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC(Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, Ep CAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outsidein signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as mi RNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows PaCSC exosomes(TEX) to reprogram neighboring nonCSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX.

Dynamic glial response and crosstalk in demyelination-remyelination and neurodegeneration processes

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system.It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes.Glial cells(microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis.Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process.A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration.This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models.In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell-and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

Adipose-brain crosstalk: do adipokines have a role in neuroprotection?

Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.

脊髓缺血再灌注损伤后的免疫炎性微环境

背景:脊髓缺血再灌注损伤后炎性微环境的变化影响着损伤修复和预后。目的:对脊髓缺血再灌注损伤后炎性微环境研究进展进行综述。方法:以“spinal cord ischemia-reperfusion,inflammaion,Microglia,Astrocytes,Macrophages,Crosstalk”为英文检索词,以“脊髓缺血再灌注损伤,炎症,小胶质细胞,星形胶质细胞,巨噬细胞,细胞交互”为中文检索词,检索发表在PubMed、CNKI、万方数据库的相关文献,最终纳入42篇文献进行综述分析。结果与结论:免疫炎性微环境的变化对脊髓缺血再灌注损伤后神经细胞损伤和修复具有调控作用,如小胶质细胞通过活化为M1/M2表型来调控炎症反应抵御传染源、清除凋亡和受损细胞、重塑不适当的神经连接从而帮助神经系统恢复稳态;星形胶质细胞在炎症因子的刺激下通过活化为A1/A2表型调控免疫过程来维持中枢神经系统稳态和神经元功能;以及巨噬细胞通过活化为M1/M2型来调控免疫过程修复损伤的脊髓组织,它们互相影响着彼此,如小胶质细胞和星形胶质细胞彼此也相互影响,如脊髓损伤时,小胶质细胞最先活化并释放炎症因子诱导星形胶质细胞激活,释放相应的细胞因子、趋化因子、Ca2+等来调节小胶质细胞的表型和功能,通过维持免疫炎性微环境稳态才是脊髓缺血再灌注损伤治疗的关键。

黄芪-莪术对Lewis肺癌小鼠肿瘤血管及肿瘤微环境中CD8^(+)T细胞的影响

目的 通过观察黄芪-莪术对肿瘤血管及肿瘤微环境中CD8^(+)T细胞及IFN-γ的影响,探讨黄芪-莪术促进肿瘤血管正常化的作用及其与调控CD8^(+)T细胞分化和IFN-γ释放的关系。方法 采用Lewis肺癌移植瘤小鼠模型,分为模型组、贝伐单抗组、PD-1抗体组与黄芪-莪术组共4组,每组各10只,分别给予无药溶剂或相应药物,连续14 d。第14天给药后超声造影观测各组小鼠肿瘤组织血流灌注情况,第15天取材经免疫荧光观测肿瘤组织血管结构,流式细胞术检测肿瘤组织中CD8^(+)T细胞情况,酶联免疫吸附试验检测肿瘤组织内免疫因子干扰素-γ(Interferon-γ,IFN-γ)、白介素-2(Interleukin-2,IL-2)及血管内皮生长因子A(Vascular endothelial growth factor A,VEGFA)、促血管生成素-2(Angiopoietin-2,Ang-2)、基质金属蛋白酶-9(Matrix metalloprotein-9,MMP-9)和整合素αvβ3(Intergrin αvβ3)含量,进行统计学分析。结果 与模型组比较,各用药组肿瘤体积增长较为缓慢(P<0.05),而黄芪-莪术组与贝伐单抗组相当,均优于PD-1抗体组(P<0.05)。超声检测显示,与模型组比较,各用药组肿瘤组织内造影剂呈现快进快出,黄芪-莪术组及贝伐单抗组与模型组比较上升支斜率大、达峰时间短,差异有统计学意义(P<0.05),说明血流灌注增速;黄芪-莪术组较PD-1抗体组上升支斜率大、达峰时间短(P<0.05),贝伐单抗组较PD-1抗体组达峰时间短(P<0.05)。免疫荧光检测显示,与模型组比较,各用药组肿瘤组织微血管密度降低、周细胞覆盖率提升(P<0.05)。流式细胞术检测显示,与模型组比较,黄芪-莪术组与PD-1抗体组CD28^(+)TCF^(+)细胞和CD8^(+)IFN-γ^(+)细胞比例均增加(P<0.05),贝伐单抗组较模型组CD28^(+)TCF^(+)细胞和CD8^(+)IFN-γ^(+)细胞比例增加,但差异无统计学意义(P>0.05);与贝伐单抗组比较,黄芪-莪术组升高CD8^(+)IFN-γ^(+)细胞比例更多(P<0.05),PD-1抗体组升高CD28^(+)TCF^(+)细胞比例更多(P<0.05);与PD-1抗体组比较,黄芪-莪术组CD28^(+)TCF^(+)细胞比例较低,CD8^(+)IFN-γ^(+)细胞比例较高,但差异均无统计学意义(P>0.05)。ELISA检测结果显示,与模型组比较,除贝伐单抗组IL-2水平外差异无统计学意义(P>0.05),各用药组肿瘤组织内VEGFA、Ang-2、整合素αvβ3、MMP-9水平均降低(P<0.01),免疫因子IFN-γ、IL-2水平均升高(P<0.05)。结论 黄芪-莪术能促进肿瘤血管正常化,抑制肿瘤生长,其机制可能与其促进肿瘤微环境中CD8^(+)T细胞向CD28^(+)TCF^(+)细胞分化、增加CD8^(+)IFN-γ^(+)细胞比例和IFN-γ含量有关。

鸡卵泡选择及分子调控作用机制研究进展

鸡卵泡选择能否有序进行是直接影响等级卵泡数量以及产蛋持续性的重要因素。本文主要综述了家禽卵泡选择发育过程及其影响因素,并提炼阐述卵泡选择过程中颗粒细胞的作用,以及各信号通路之间的串扰调控功能,丰富禽类繁殖调控基础理论,为鸡的繁殖调控研究提供参考价值。

Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer

Background:Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy.However,the unique features of the immune microenvironment of triple negative breast cancer(TNBC)compared with other subtypes of breast cancer remain elusive.Therefore,we aimed to depict and compare the immune landscape among TNBC,human epidermal growth factor receptor 2-positive(HER2^(+))breast cancer,and luminal-like breast cancer.Methods:Single-cell RNA sequencing(scRNA-seq)was performed on CD45^(+)immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes.By analyzing the scRNA-seq data,immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC,human HER2^(+)breast cancer,and luminal-like breast cancer.Pseudotime and cell-cell communication analyses were also conducted to characterize the immune microenvironment.Results:ScRNA-seq data of 117,958 immune cells were obtained and 31 immune clusters were identified.A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2^(+)or luminal-like breast cancer,which was characterized by higher proportions of regulatory T cells(Tregs)and exhausted CD8+T cells and accompanied by more abundant plasma cells.Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores.Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC.Cell-cell communication analyses indicated that these unique features are fostered by the diversified T cell-B cell crosstalk in TNBC.Based on the T cell-B cell crosstalk,a prognostic signaturewas established that could effectively predict the prognosis status for patients with TNBC.Additionally,it was found that TNBC had a higher proportion of cytotoxic natural killer(NK)cells,whereas HER2^(+)or luminal-like breast cancer lost this feature,suggesting thatHER2^(+)or luminal-like breast cancer,but not TNBC,may benefit from NK-based immunotherapy.Conclusions:This study identified a distinct immune feature fostered by T cell-B cell crosstalk in TNBC,which provides better prognostic information and effective therapeutic targets for breast cancer.