肿瘤相关巨噬细胞研究进展

单核巨噬细胞是一种多功能细胞,对不同的微环境信号应答表现出不同的功能.而极化的M1和M2巨噬细胞是巨噬细胞功能表现的两个极端.其中侵润到肿瘤组织的巨噬细胞受肿瘤诱导产生的细胞因子的影响使巨噬细胞表现出巨噬细胞M2型表型,这些极化的巨噬细胞在破坏适应性免疫反应和促进肿瘤生长与进展方面具有重要作用.肿瘤相关巨噬细胞(TAM)可以促进肿瘤进展包括促进肿瘤生长、侵润、转移,促进血管生长和免疫抑制等,因而研究TAM具有重要意义.     

肿瘤相关巨噬细胞研究进展

单核巨噬细胞是一种多功能细胞,对不同的微环境信号应答表现出不同的功能.而极化的M1和M2巨噬细胞是巨噬细胞功能表现的两个极端.其中侵润到肿瘤组织的巨噬细胞受肿瘤诱导产生的细胞因子的影响使巨噬细胞表现出巨噬细胞M2型表型,这些极化的巨噬细胞在破坏适应性免疫反应和促进肿瘤生长与进展方面具有重要作用.肿瘤相关巨噬细胞(TAM)可以促进肿瘤进展包括促进肿瘤生长、侵润、转移,促进血管生长和免疫抑制等,因而研究TAM具有重要意义.     

肿瘤相关巨噬细胞研究进展

单核巨噬细胞是一种多功能细胞,对不同的微环境信号应答表现出不同的功能。而极化的MI和M2巨噬细胞是巨噬细胞功能表现的两个极端。其中侵润到肿瘤组织的巨噬细胞受肿瘤诱导产生的细胞因子的影响使巨噬细胞表现出巨噬细胞M2型表型,这些极化的巨噬细胞在破坏适应性免疫反应和促进肿瘤生长与进展方面具有重要作用。肿瘤相关巨噬细胞（TAM）可以促进肿瘤进展包括促进肿瘤生长、侵润、转移,促进血管生长和免疫抑制等,因而研究TAM具有重要意义。     

色素上皮源性因子与肿瘤

色素上皮源性因子 (Pigmentepithelium derivedfactor ,PEDF)是一种存在于正常组织中的可溶性糖蛋白。它具有营养和保护神经、抑制血管形成、促进肿瘤分化和凋亡等功能。PEDF是近年来国外研究较多的肿瘤生长和转移抑制因子之一 ,它的发现和其对肿瘤作用机制的阐明 ,对于人类恶性肿瘤的基础研究和临床应用具有重要的意义。     

Vasohibin-1在常见肿瘤发生发展中作用的研究进展

肿瘤的形成、生长和侵袭转移依赖于肿瘤血管的生成。抑制肿瘤血管形成是阻止肿瘤进展的重要途径。肿瘤血管的生长受多种促进因子(如血管内皮生长因子、碱性成纤维细胞生长因子、胸苷磷酸化酶等)和抑制因子(如血管抑素、内皮抑素、血管生成抑制蛋白等)的共同调节。Vasohibin-1(VASH-1)作为一种新型血管抑制因子,受VEGF诱导表达于内皮细胞,发挥负性调控作用。近年来越来越多的研究发现VASH-1在多种肿瘤组织中异常表达并发挥作用。该文旨在对VASH-1在一些常见肿瘤发生、发展中的作用及机制作一综述。     

肥大细胞与肿瘤关系

作为间质结缔组织中的一种恒定的细胞成分——肥大细胞被喻为多功能细胞因子之源 [1 ]。它不仅作为一种免疫效应细胞参与速发型变态反应 ,还与许多疾病包括肿瘤性疾病的病理过程有关。近年来 ,有关肥大细胞与肿瘤关系的研究越来越受到重视。本文主要拟就肥大细胞在肿瘤内的分布及形态学表现 ,肥大细胞对肿瘤生长的影响 ,肥大细胞分泌的生物活性物质对肿瘤生长的可能抑制机制等几个方面作一综述。     

Semaphorins与肿瘤的发生和转移

Semaphorins是一大类具有保守Sema结构域的信号蛋白。该家族分为8个亚群，目前已发现30多个成员，有分泌型、跨膜型和GPI锚定3种类型。在病毒、非脊椎动物和脊椎动物中都已发现Semaphorins分子的存在。该家族蛋白主要有2种受体：plexins和neuropilins，它们对Semaphorins功能的发挥非常重要。Semaphorins首先是作为神经系统中一种重要的神经导向分子而被发现和认识的。起初的研究多围绕其在神经系统轴突导向中所发挥的作用而进行，发现Semaphorins分子可以抑制或促进轴突的生长。但现在越来越多的研究表明，除了在神经系统中具有重要作用外，Semaphorins分子在肿瘤生长、血管内皮细胞迁移、免疫反应等方面也有重要的生物学功能。Semaphorins分子通过促进或抑制肿瘤血管发生而对肿瘤的发生发展进行调节。     

肥大细胞在细菌和病毒感染中的作用

自1878年发现肥大细胞以来，人们对肥大细胞在过敏性疾病中的作用进行了广泛而深入的研究，但对肥大细胞的生理功能却了解不多。从无脊椎动物的昆虫到人类，肥大细胞在生物体的长期进化中能得以保留，说明这种细胞具有不可替代的重要作用。肥大细胞广泛分布于皮肤、呼吸道和胃肠道等易与外界接触的部位，并位于血管周围。这就使得肥大细胞不仅能时刻监视病原菌的入侵，而且肥大细胞所释放的介质和细胞因子也能迅速作用于血管内皮细胞和血液中的炎性细胞，并经血液分布到全身各组织器官中。有关肥大细胞在宿主抵御病原微生物中的作用已引起人们的关注。本综述主要介绍肥大细胞在细菌感染时，对宿主的保护和损伤作用、对细菌识别的分子机制以及肥大细胞与病毒感染等方面的研究进展。     

IL-17在肿瘤发生发展中的作用

Th17作为新发现的一类Th细胞亚群,其分泌的IL-17在肿瘤的发生与发展过程中有着重要的作用.大量文献报道IL-17在肿瘤发生发展过程中发挥双刃剑的作用,一方面,IL-17可以通过促进血管生成和肿瘤细胞的迁移促进肿瘤的生长.另一方面,IL-17亦可促进细胞毒性T细胞的免疫应答抑制肿瘤的生长.     

中药与血管生成的研究进展

血 管的生成在许多疾病的发生发展及转归、预后中扮演着重要的角色。近年来 ,调节血管生成的研究已成为临床治疗中的热点。研究主要集中在两个方面 :①抑制血管生成的研究。许多疾病的发生、发展与血管生成有着密切的关系 ,如恶性肿瘤在其生长过程中 ,肿瘤组织中不断有新生血管生成 ,这些新生血管为肿瘤的生长提供了丰富的血供和营养。同时 ,由于新生血管管壁较薄 ,肿瘤细胞易于穿过 ,从而进入血循环发生远处转移。因此 ,如能抑制新生血管的生成 ,也就可以阻断肿瘤血供 ,达到“饿死”癌细胞的目的。其他一些良性疾病 ,如类风湿关节炎、眼底…     

Role of mast cells in tumor growth

The growth of malignant tumors is determined in large part by the proliferative capacity of the tumor cells. Clinical observations and animal experiments have established that tumor cells elicit immune responses. Histopathologic studies show that many tumors are surrounded by mononuclear cell and mast cell infiltrates. Mast cells are ubiquitous in the body and are critical for allergic reactions. Increasing evidence indicates that mast cells secrete proinflammatory cytokines and are involved in neuro-inflammatory processes and cancer. Mast cells accumulate in the stroma surrounding certain tumors, especially mammary adenocarcinoma, and the molecules they secrete can benefit the tumor. However, mast cells can also increase at the site of tumor growth and participate in tumor rejection. Mast cells may be recruited by tumor-derived chemoattractants and selectively secrete molecules such as growth factors, histamine, heparin, VEGF, and IL-8, as well as proteases that permit the formation of new blood vessels and metastases. Tumor mast cell intersections play regulatory and modulatory roles affecting various aspects of tumor growth. Discovery of these new roles of mast cells further complicates the understanding of tumor growth. This review focuses on the strategic importance of mast cells to the progression of tumors, and proposes a revised immune effector mechanism of mast cell involvement in tumor growth.     

The contribution of mast cells to bacterial and fungal infection immunity

Mast cells are hematopoietic progenitor-derived, granule-containing immune cells that are widely distributed in tissues that interact with the external environment, such as the skin and mucosal tissues. It is well-known that mast cells are significantly involved in IgE-mediated allergic reactions, but because of their location, it has also been long hypothesized that mast cells can act as sentinel cells that sense pathogens and initiate protective immune responses. Using mast cell or mast cell protease-deficient murine models, recent studies by our groups and others indicate that mast cells have pleiotropic regulatory roles in immunological responses against pathogens. In this review, we discuss studies that demonstrate that mast cells can either promote host resistance to infections caused by bacteria and fungi or contribute to dysregulated immune responses that can increase host morbidity and mortality. Overall, these studies indicate that mast cells can influence innate immune responses against bacterial and fungal infections via multiple mechanisms. Importantly, the contribution of mast cells to infection outcomes depends in part on the infection model, including the genetic approach used to assess the influence of mast cells on host immunity, hence highlighting the complexity of mast cell biology in the context of innate immune responses.     

Mast cells as modulators of T-cell responses

Summary:  Although mast cells have long been considered the integral effector cell in allergy and atopic disease, the paradigm of mast cell function is now evolving to incorporate data showing that mast cells make innumerable contributions to both protective and pathologic immune responses. Mast cells express cell surface molecules with costimulatory or co-inhibitory activity and produce a multitude of mediators that can direct dendritic cell (DC) or T-cell differentiation and function. In addition, mast cells exhibit a widespread distribution and are in close proximity to DCs and T cells at several critical sites. While there has been amazing progress in characterizing mast cell populations in vitro , only recently has the ability to monitor their in vivo effects become a reality. In this review, we discuss the evolution of our understanding of mast cell biology with an emphasis on their established and hypothesized roles in influencing T-cell differentiation and function. The fact that T-cell and mast cell interactions exist and are a normal component of most adaptive immune responses is one of the best illustrations of the now established concept that innate and adaptive immunity are not completely independent entities.     

New developments in mast cell biology

Mast cells can function as effector and immunoregulatory cells in immunoglobulin E-associated allergic disorders, as well as in certain innate and adaptive immune responses. This review focuses on exciting new developments in the field of mast cell biology published in the past year. We highlight advances in the understanding of FcvarepsilonRI-mediated signaling and mast cell-activation events, as well as in the use of genetic models to study mast cell function in vivo. Finally, we discuss newly identified functions for mast cells or individual mast cell products, such as proteases and interleukin 10, in host defense, cardiovascular disease and tumor biology and in settings in which mast cells have anti-inflammatory or immunosuppressive functions.     

Mast cells as targets for immunotherapy of solid tumors

Mast cells have historically been studied mainly in the context of allergic disease. In recent years, we have come to understand the critical importance of mast cells in tissue remodeling events and their role as sentinel cells in the induction and development of effective immune responses to infection. Studies of the role of mast cells in tumor immunity are more limited. The pro-tumorigenic role of mast cells has been widely reported. However, mast cell infiltration predicts improved prognosis in some cancers, suggesting that their prognostic value may be dependent on other variables. Such factors may include the nature of local mast cell subsets and the various activation stimuli present within the tumor microenvironment. Experimental models have highlighted the importance of mast cells in orchestrating the anti-tumor events that follow immunotherapies that target innate immunity. Mast cells are long-lived tissue resident cells that are abundant around many solid tumors and are radiation resistant making them unique candidates for combined treatment modalities. This review will examine some of the key roles of mast cells in tumor immunity, with a focus on potential immunotherapeutic interventions that harness the sentinel role of mast cells.     

The ingenious mast cell: Contemporary insights into mast cell behavior and function

Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells, and epithelial cells. During recent years, clinical and experimental studies on human mast cells, as well as experiments using animal models, have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review, we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity, and reactivity. We also highlight the development in our understanding of mast cell-driven diseases and discuss the development of novel strategies to treat such conditions.     

Mast cells and cutaneous malignancies.

This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.     

Mast cells: not only in allergy

The past decade has confronted us with a striking abundance of novel findings regarding the roles of mast cells in immune responses in health and disease. Newly developed models and techniques have enabled clear-cut dissection of the mast cell contribution in these settings. We now understand that mast cells possess critical effector functions not only within the traditional context of allergic reactions. It is likely that mast cells played pivotal roles in primitive immune systems, yet these functions have been masked in the recent eras by newer immune functions, such as adaptive immunity. Conceivably, mast cells should be refocused on so as to obtain new insights about diverse pathologic conditions, ultimately leading to novel therapeutic approaches targeting these fascinating cells.     

Transcriptional regulation of mast cell and basophil lineage commitment

Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports that basophils and mast cells have important roles in immune regulations, host defense against bacteria and viruses, and autoimmune diseases. However, origin and molecular regulation of basophil and mast cell differentiation remain incompletely understood. In this review, we focus on recent advances in the understanding of origin and molecular regulation of mouse and human basophil and mast cell development. A more complete understanding of how basophils and mast cells develop at the molecular level will lead to development of interventions that are more effective in achieving long-term success.     

Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity

Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy.