CD47分子在弥漫大B细胞淋巴瘤肿瘤微环境中的研究进展

弥漫大B细胞淋巴瘤（DLBCL）是成年人常见的高度侵袭性恶性血液肿瘤。DLBCL为一种高度异质性淋巴瘤,患者在分子生物学特征、临床表现和预后方面均存在巨大差异。目前越来越多的证据表明,肿瘤微环境对DLBCL的发生、发展发挥着重要的作用。CD47分子是一种整合素相关蛋白,在DLBCL细胞中过度表达,并在淋巴瘤免疫逃逸中起关键作用。本文拟就CD47分子相关信号通路、在DLBCL肿瘤微环境中的作用和DLBCL中靶向CD47分子的治疗策略等方面的研究进展进行综述。     

热疗对肿瘤微环境中肿瘤相关成纤维细胞作用的研究进展

肿瘤微环境具有免疫抑制特性, 其作用机制是诱导肿瘤细胞的免疫逃逸, 它与肿瘤细胞之间的相互作用是影响肿瘤发生发展的重要因素。肿瘤相关成纤维细胞是肿瘤微环境的一个重要组成部分, 其主要功能是与肿瘤细胞发生直接或间接的相互作用, 并产生各种细胞因子, 从而对肿瘤免疫微环境起到调节作用。肿瘤热疗作为抗肿瘤治疗的一种手段, 随着对肿瘤热疗和肿瘤微环境的研究不断深入, 大量研究发现热疗对肿瘤微环境中的肿瘤相关成纤维细胞具有多种调节功能。本文结合国内外最新研究进展, 阐述热疗对肿瘤微环境中肿瘤相关成纤维细胞及其相关细胞和因子的影响, 为肿瘤热疗结合免疫或靶向治疗的临床应用提供新途径。     

热疗对肿瘤微环境中肿瘤相关成纤维细胞作用的研究进展北大核心CSCD

肿瘤微环境具有免疫抑制特性,其作用机制是诱导肿瘤细胞的免疫逃逸,它与肿瘤细胞之间的相互作用是影响肿瘤发生发展的重要因素。肿瘤相关成纤维细胞是肿瘤微环境的一个重要组成部分,其主要功能是与肿瘤细胞发生直接或间接的相互作用,并产生各种细胞因子,从而对肿瘤免疫微环境起到调节作用。肿瘤热疗作为抗肿瘤治疗的一种手段,随着对肿瘤热疗和肿瘤微环境的研究不断深入,大量研究发现热疗对肿瘤微环境中的肿瘤相关成纤维细胞具有多种调节功能。本文结合国内外最新研究进展,阐述热疗对肿瘤微环境中肿瘤相关成纤维细胞及其相关细胞和因子的影响,为肿瘤热疗结合免疫或靶向治疗的临床应用提供新途径。     

脂肪酸代谢影响肿瘤免疫微环境与免疫治疗的研究进展

肿瘤免疫微环境是肿瘤细胞周围的微小结构,对肿瘤的发生、发展起着重要作用,也是多种免疫治疗靶向的核心区域, 其调控因素非常复杂。肿瘤免疫微环境中存在促进免疫耐受和肿瘤免疫逃逸的多种调控机制,除免疫检查点分子上调、抗原提 呈丢失等过程外,还包括免疫细胞的代谢重编程。免疫细胞的脂肪酸代谢是肿瘤免疫微环境的关键代谢过程,受肿瘤细胞的信 号调控和营养争夺影响可发生重编程,其在肿瘤免疫治疗中的调控规律是目前新兴的研究热点。本文集中回顾了脂肪酸代谢对 肿瘤免疫微环境中效应T细胞、记忆T细胞、调节性T细胞、肿瘤相关巨噬细胞等免疫细胞生存和功能的调节机制,讨论了近年来 免疫细胞脂肪酸代谢重编程影响免疫检查点阻断治疗、过继细胞治疗、肿瘤治疗性疫苗等免疫治疗效果的最新进展,总结了新近 出现的免疫相关的脂肪酸代谢调控靶点和相关药物,指出肿瘤相关免疫细胞脂肪酸代谢的独有特点和研究难点,为肿瘤免疫治 疗提供新的思路和见解。     

鼻咽癌与免疫逃逸

肿瘤的免疫逃逸是癌症的一大特征,目前所知的肿瘤逃逸机制主要包括肿瘤的直接免疫逃逸和肿瘤微环境介导的免疫逃逸.鼻咽癌的发生发展与其肿瘤细胞的免疫逃逸密切相关,其中与鼻咽癌相关的肿瘤的直接免疫逃逸主要包括肿瘤细胞表面主要组织相容性复合体-Ⅰ类分子表达下降或缺失、肿瘤细胞缺乏共刺激分子以及Fas/FasL系统介导的免疫逃逸;与鼻咽癌相关的肿瘤微环境介导的免疫逃逸则包括肿瘤相关免疫抑制分子和肿瘤相关免疫抑制性细胞.研究鼻咽癌免疫逃逸的作用机制能够为其治疗及预防提供新的研究方向.     

套细胞淋巴瘤免疫微环境与免疫治疗研究进展

套细胞淋巴瘤(mantle cell lymophoma, MCL)是非霍奇金淋巴瘤的一种罕见亚型,难以治愈且复发率高,预后较差。随着对肿瘤免疫微环境认识的逐步深入,微环境在恶性肿瘤中的关键作用引起广泛关注。近年来微环境参与套细胞淋巴瘤发生发展机制引起重视。对套细胞淋巴瘤免疫微环境组成及功能的阐释推动了抗肿瘤免疫治疗领域的探索,并在嵌合抗原受体T细胞疗法、肿瘤疫苗、免疫调节剂治疗中取得重要进展。该文针对套细胞淋巴瘤免疫微环境及免疫治疗进展作一综述。     

吲哚胺 2，3-双加氧酶与淋巴瘤关系的研究进展

淋巴瘤是一组常见的淋巴造血系统肿瘤,免疫耐受在其发生发展中具有重要的作用。 吲哚胺 2,3-双加氧酶( indoleamine 2,3-dioxygenase,IDO)是细胞内色氨酸分解的限速酶,肿瘤微环境中,IDO活性增高,导致区域色氨酸耗竭,代谢产物犬尿氨酸蓄积,抑制效应T细胞和自然杀伤（natural killer,NK）细胞增殖和功能,激活调节性T( regulatory T,Treg)细胞,产生免疫逃逸,从而促进淋巴瘤的发生与发展。 本文阐述了IDO的生物学特性、与免疫逃逸关系,并对 IDO 在淋巴瘤的预后及治疗中的作用进行了综述。     

树突状细胞分化成熟障碍在肺癌免疫逃逸中的研究

肺癌患者体内存在广泛的免疫逃逸现象,这一事实已在鼠肿瘤模型及癌症患者得到确认.目前所知肺癌免疫逃逸的机制很多,其中树突状细胞(DC)的分化成熟异常导致的功能障碍是肿瘤免疫逃逸的主要机制之一,肺癌微环境已成为造成DC功能不足的重要因素.     

皮肤T细胞淋巴瘤的恶性炎症及肿瘤微环境的研究进展

T细胞淋巴瘤属非霍奇金亚型中的集合型淋巴瘤,是非常罕见的恶性肿瘤。研究结果显示该病预后较差。近年关于慢性炎症与肿瘤发生相关性的研究日益增多,炎症微环境和促炎因子的变化等因素可诱发肿瘤的进展,同时提示了较差的预后。目前,关于慢性炎症与实体肿瘤发生的相关性研究较多,而关于引发炎症的细胞通过异常活化推动恶性转化过程相关研究报导较少。皮肤T细胞淋巴瘤（CTCL）的特征之一是存在长期发炎的含有恶性T细胞的皮肤损伤。本文针对皮肤T细胞淋巴瘤的免疫-炎症微环境,对近两年的研究进行综述。     

乳酸对肿瘤微环境内免疫细胞的影响及相关靶点治疗的研究进展

肿瘤代谢与肿瘤免疫关系复杂多样，同时肿瘤细胞代谢重编程塑造特异性的肿瘤微环境，其在肿瘤免疫治疗方面的作用尚未解释清楚。乳酸是糖酵解的主要产物，肿瘤细胞的有氧糖酵解使乳酸在微环境内堆积。近年来，大量研究表明，肿瘤微环境内堆积的乳酸对抗肿瘤免疫造成阻碍，尤其影响了免疫细胞的功能、分化和代谢以及参与肿瘤免疫逃逸等，发挥着促肿瘤作用。本文回顾了肿瘤微环境内乳酸堆积对树突状细胞、T细胞、NK细胞、肿瘤相关巨噬细胞及髓源性抑制细胞的影响。靶向干预肿瘤细胞产生及外排乳酸的过程有望成为肿瘤免疫治疗的新策略。     

Immune microenvironment profiles of tumor immune equilibrium and immune escape states of mouse sarcoma

Cancer immunoediting consists of three distinct phases: elimination, equilibrium and escape. Here, for the first time, we investigated the immune microenvironment profiles of tumor immune equilibrium and immune escape states in 3′-methylcholanthrene-induced murine sarcoma model. Our study indicates the relative balance of monocytic MDSCs and antitumor immunity cells (especially CTLs, NK cells and γδT cells) may involve in maintaining tumor cells in a state of immune-mediated dormancy. In addition, high percentages of Treg cells and PMN-MDSCs are associated with the tumor immune escape state – mice with progressing sarcomas. In summary, the relative balance of immune effector cells and suppressive populations in the tumor microenvironment may involve in determining the fate of tumors.     

调节性免疫细胞在多发性骨髓瘤中的临床价值研究进展

多发性骨髓瘤（multiple myeloma,MM）是骨髓浆细胞恶性增殖性疾病。尽管新药的出现显著改善了MM患者的预后,复发与耐药的问题仍有待解决,深入分析MM免疫微环境可能是潜在的突破口。免疫抑制微环境的形成是MM的突出特征,导致抗肿瘤免疫监视受损,恶性浆细胞发生免疫逃逸。调节性免疫细胞是免疫抑制微环境形成的重要因素,与MM的发病、进展和耐药密切相关。随着MM进入免疫治疗时代,调节性免疫细胞在MM诊断、治疗和预后中的价值逐渐被发现,其数量或比例变化可能有助于MM早期诊断和预后评估,并有望成为新的治疗靶点。本文将对调节性免疫细胞在MM临床诊治中的研究进展进行综述。      

Tumor-driven evolution of immunosuppressive networks during malignant progression

Tumors evolve mechanisms to escape immune control by a process called immune editing, which provides a selective pressure in the tumor microenvironment that could lead to malignant progression. A variety of tumor-derived factors contribute to the emergence of complex local and regional immunosuppressive networks, including vascular endothelial growth factor, interleukin-10, transforming growth factor-beta, prostaglandin E(2), and soluble phosphatidylserine, soluble Fas, soluble Fas ligand, and soluble MHC class I-related chain A proteins. Although deposited at the primary tumor site, these secreted factors could extend immunosuppressive effects into the local lymph nodes and the spleen, promoting invasion and metastasis. Vascular endothelial growth factors play a key role in recruiting immature myeloid cells from the bone marrow to enrich the microenvironment as tumor-associated immature dendritic cells and tumor-associated macrophages. The understanding of the immunosuppressive networks that evolve is incomplete, but several features are emerging. Accumulation of tumor-associated immature dendritic cells may cause roving dendritic cells and T cells to become suppressed by the activation of indoleamine 2,3-dioxygenase and arginase I by tumor-derived growth factors. Soluble phosphatidylserines support tumor-associated macrophages by stimulating the release of anti-inflammatory mediators that block antitumor immune responses. Soluble Fas, soluble FasL, and soluble MHC class I-related chain A proteins may help tumor cells escape cytolysis by cytotoxic T cells and natural killer cells, possibly by counterattacking immune cells and causing their death. In summary, tumor-derived factors drive the evolution of an immunosuppressive network which ultimately extends immune evasion from the primary tumor site to peripheral sites in patients with cancer.     

CD47在淋巴瘤治疗中的研究进展

CD47作为一种跨膜蛋白,广泛分布于多种细胞,通过与巨噬细胞上信号调节蛋白α（SIRPα）结合,释放抑制信号,逃避巨噬细胞的吞噬。淋巴瘤细胞CD47表达上调是诱导免疫逃逸的重要机制之一,也是潜在的治疗靶点。文章就CD47诱导的免疫逃逸、靶向CD47的单克隆抗体和细胞免疫治疗等治疗手段在淋巴瘤治疗中的研究进展进行综述。     

非小细胞肺癌发生、发展过程中免疫微环境变化及其临床意义

免疫系统在肿瘤的发生、发展中起着双重作用,它可以识别并消灭肿瘤细胞,肿瘤细胞也可以在免疫选择的压力下利用免疫系统自身负调控机制形成复杂的免疫抑制网络,逃避宿主免疫攻击。非小细胞肺癌（non-small cell lung cancer,NSCLC）的免疫微环境不断变化,具有异质性,这种异质性来源于多种因素的相互作用,包括肿瘤分子亚型、驱动基因及拷贝数变异等。微环境中免疫细胞数量、密度、种类、功能状态、空间分布与NSCLC的发生、发展、预后及抗肿瘤免疫应答密切相关。本文综述了NSCLC发生、发展过程中免疫微环境变化及其临床意义,以进一步理解免疫系统在NSCLC中的作用。     

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.     

The tumor microenvironment and its role in promoting tumor growth

The tumor microenvironment is created by the tumor and dominated by tumor-induced interactions. Although various immune effector cells are recruited to the tumor site, their anti-tumor functions are downregulated, largely in response to tumor-derived signals. Infiltrates of inflammatory cells present in human tumors are chronic in nature and are enriched in regulatory T cells (T(reg)) as well as myeloid suppressor cells (MSC). Immune cells in the tumor microenvironment not only fail to exercise antitumor effector functions, but they are co-opted to promote tumor growth. Sustained activation of the NF-kappaB pathway in the tumor milieu represents one mechanism that appears to favor tumor survival and drive abortive activation of immune cells. The result is tumor escape from the host immune system. Tumor escape is accomplished through the activation of one or several molecular mechanisms that lead to inhibition of immune cell functions or to apoptosis of anti-tumor effector cells. The ability to block tumor escape depends on a better understanding of cellular and molecular pathways operating in the tumor microenvironment. Novel therapeutic strategies that emerge are designed to change the pro-tumor microenvironment to one favoring acute responses and potent anti-tumor activity.     

CAR-T疗法在治疗肿瘤免疫逃逸中的研究进展

机体内的免疫系统可以对肿瘤细胞产生免疫应答从而进一步消除肿瘤。但部分肿瘤能在宿主体内生长、转移和突变,表明其具有免疫逃逸的能力。肿瘤细胞抗原本身发生逃逸、效应细胞功能强弱、肿瘤细胞微环境等都与肿瘤的免疫逃逸密切相关。近年来,以嵌合抗原受体T（CAR-T）细胞疗法为主的免疫疗法在肿瘤的治疗领域发展迅猛,正逐渐成为治疗肿瘤的主流方向,本文对治疗肿瘤免疫逃逸中CAR-T的应对治疗策略和进展进行梳理,旨在为CAR-T疗法治疗肿瘤的下一步发展优化思路。