光动力疗法治疗肿瘤的免疫机制研究进展

光动力疗法(photodynamic therapy,PDT)是治疗肿瘤的有效手段之一,PDT治疗可导致肿瘤细胞的死亡和凋亡,并损伤肿瘤相关血管.近年来,PDT的免疫机制越来越受到关注.肿瘤细胞的免疫逃逸是肿瘤发生发展的重要因素.PDT治疗肿瘤时,可通过免疫原性细胞死亡(immunogenic cell death,ICD)诱导肿瘤细胞表达损伤相关分子模式(damage associated molecular patterns,DAMPs),从而活化树突状细胞,诱导机体特异性抗肿瘤免疫.同时,PDT还可影响肿瘤微环境中的相关免疫细胞和因子,进而增强机体抗肿瘤反应.光动力治疗和其他免疫治疗联合应用亦能增强疗效.故光动力治疗的免疫机制研究将为肿瘤治疗提供可能的新思路.     

纳米药物递送系统在肿瘤免疫治疗中的研究进展北大核心CSCD

目的:肿瘤免疫疗法通过激发和增强机体的免疫应答来发挥抗肿瘤作用,成为继外科手术、化疗、放疗之后又一类具有显著临床治疗效果及优势的抗肿瘤疗法。多种类型的免疫治疗药物相继涌现,但药物的体内递送仍面临诸多挑战,如较差的肿瘤渗透性和较低的肿瘤细胞摄取率等。随着近年来纳米科技的发展,纳米技术已经广泛应用于医学、药学和生物学等领域。纳米药物递送系统能够提高免疫治疗药物在肿瘤部位的滞留、蓄积、渗透及靶细胞摄取,并实现其在肿瘤胞外基质或肿瘤细胞内的可控释放,提高调控抗肿瘤免疫反应的效率,增强肿瘤免疫治疗效果。本文总结并阐述了近年来纳米药物递送系统在肿瘤免疫治疗研究领域取得的成果,也对该领域的主要挑战和发展方向进行了展望。     

用于肿瘤联合治疗的基因和化疗药物纳米共载体系的研究进展

化学药物治疗（化疗）或基因治疗单独使用治疗肿瘤均具有较多缺陷,而将两者联合应用能协同治疗肿瘤,克服单一疗法的不足.纳米载体既能包载化疗药物又能递送基因,其用于肿瘤的联合治疗,可减少化疗药物的剂量,增加药物在靶器官的分布量,减轻毒副作用,从而提高抗肿瘤效果;同时保护携带基因的稳定性和完整性,一定程度上提高基因的转染效率,以达到减轻毒副作用及提高疗效的协同目的.基因和化疗药物纳米共载体系用于肿瘤的联合治疗是近年来肿瘤治疗的研究热点.就基因和化疗药物纳米共载体系的类型及负载基因类型,特别是纳米共载体系用于肿瘤联合治疗的研究进行总结和展望.     

减毒沙门菌作为新型肿瘤疫苗运送载体——癌症免疫治疗新希望

抗肿瘤免疫治疗是通过提高肿瘤特异性抗原的免疫原性及肿瘤细胞对效应性杀伤细胞的敏感性,调动机体免疫系统抵抗肿瘤细胞增殖和浸润的免疫治疗方法.与常规手术治疗、放射治疗和化学药物治疗相比,免疫治疗具有伤害小、毒性低等优点,但其在疫苗策略领域中的效果并不理想.近年来的研究表明,适当的载体有望显著提高疫苗的效果.减毒沙门菌是一种活疫苗载体,具有佐剂的作用,能够有效激活机体免疫细胞,在抗肿瘤免疫治疗中具有广阔的应用前景.     

阻断CLTA-4/PD-1联合化疗药物在肿瘤治疗中的应用

化学药物治疗（化疗）是目前治疗肿瘤最有效的手段之一，但单独应用化学药物存在肿瘤靶向能力差、副作用严重、容易导致肿瘤耐药等弊端。免疫治疗是通过重新启动并维持肿瘤-免疫循环，恢复机体正常抗肿瘤免疫反应，从而控制与清除肿瘤的治疗方法。免疫检查点抑制剂（ICIs）是免疫治疗中的一类常规药物，以抗程序性死亡蛋白1(PD-1)抗体和细胞毒性T淋巴细胞抗原4(CTLA-4)抑制剂为代表。研究者发现通过阻断CLTA-4或PD-1与化疗药物联用，不仅能发挥化疗药物对肿瘤的细胞毒作用，还可通过促进淋巴细胞的增殖与活化、弥补化学治疗抑制机体免疫的弊端、促进并维持记忆T细胞增殖等一系列促进免疫系统发挥作用的方式提高抗肿瘤效果。本文对联合治疗的实验室和临床研究模式，及其作用机制进行综述。     

冷冻消融结合免疫治疗：实现抗肿瘤效应最大化

近年来，基于能量治疗的肿瘤消融技术应用愈加广泛。其中，冷冻消融技术是通过对探针的快速冷却，有效破坏肿瘤组织。然而，留在原位的肿瘤碎片还会释放出大量抗原，激活免疫细胞，诱导产生抗肿瘤免疫反应。但因冷冻消融参数条件设置的不同，会影响所触发的免疫反应，且因诱发产生的免疫反应的强度和可持续性不足，难以有效抑制肿瘤的复发和转移瘤的生长。综述冷冻消融治疗肿瘤的机制，包括直接细胞损伤、血管损伤和免疫调节，其中免疫调节对肿瘤治疗的良好预后产生重要影响；阐述影响免疫调节效果的冷冻消融因素，探寻冷冻消融治疗后产生免疫反应的最佳条件；概述冷冻消融联合免疫治疗的研究进展，并且探讨联合抗肿瘤治疗的新策略。     

光动力疗法的抗肿瘤机制及光敏剂的研究进展

光动力疗法（PDT）是利用光动力效应对疾病进行诊断与治疗的一种非侵袭性技术,已被用于临床头颈部、乳腺、肺、前列腺及皮肤等部位肿瘤的治疗.与传统治疗方法相比,PDT具有创伤小、毒性低、选择性好、适用范围广及不易产生耐药等优势,因而受到肿瘤治疗领域的广泛关注.PDT的抗肿瘤机制复杂,光敏剂是发挥其光动力学效应的关键因素之一,提高光敏剂的靶向输送和携氧能力是改善光动力疗效的重要途径.对PDT的抗肿瘤机制及光敏剂的研究进展进行综述.     

肿瘤免疫治疗的研究进展

肿瘤免疫治疗通过调动或激发机体自身的免疫功能,增强肿瘤周围微环境中各种抗肿瘤能力,从而抑制和杀伤肿瘤细胞。相对于传统的肿瘤治疗方法,肿瘤免疫治疗具有自身特有的诸多优势,也可提高传统治疗方法的疗效,减轻传统治疗方法的不良反应。本文就肿瘤相关抗原、肿瘤免疫治疗的分类、肿瘤免疫治疗与传统肿瘤治疗手段的联合应用、以及肿瘤免疫治疗的优势等方面相关的研究进展进行综述。     

GVAX肿瘤疫苗研究进展

肿瘤免疫治疗是通过调节机体的免疫功能从而达到杀灭肿瘤细胞的一种治疗手段,有望成为继手术、放疗、化疗之后第四种抗肿瘤治疗方法。根据机体抗肿瘤免疫效应机制的不同,肿瘤免疫治疗可分为主动免疫治疗和被动免疫治疗两大类。GVAX肿瘤疫苗是一种典型的肿瘤主动免疫治疗,近年来在肿瘤免疫治疗研究中已成为新的热点,并取得了不少进展。本文就GVAX瘤苗的原理,在实验动物模型及临床试验研究中的疗效、安全性、临床应用前景等内容作一综述。     

工程化纳米囊泡结合化疗用于增强肿瘤免疫治疗

目的：结合免疫治疗与化疗,以改善肿瘤的治疗效果,为安全有效的肿瘤免疫治疗策略的发展提供更多见解。方法：使用工程化纳米囊泡,囊泡膜上表达PD-1受体,可以靶向肿瘤细胞表面的PD-L1,通过破坏PD-1/PD-L1免疫抑制通路增强抗肿瘤反应。同时,囊泡包裹的化疗药物阿霉素可以进入肿瘤细胞核,抑制DNA与RNA的合成,诱导肿瘤细胞死亡。结果：实验证实,制备的PD1-阿霉素材料具备良好的稳定性、安全性,能准确靶向肿瘤部位,阿霉素在细胞核部位起作用,能有效地进行肿瘤杀伤。结论：本研究首次将PD-1免疫检查点抑制与化疗药物阿霉素相结合,利用PD-1囊泡安全性高、长循环的特点作为包裹化疗药物阿霉素的载体,这种方法可以进行肿瘤细胞的有效靶向与治疗,实现肿瘤的有效清除。     

Does chemotherapy augment anti-tumor immunotherapy by preferential impairment of regulatory T cells?

Chemotherapy, the treatment modality of choice for advanced cancers, is considered immunosuppressive due to its depletion of immune cells. Hence, chemotherapy is traditionally thought to adversely affect anti-tumor immune responses and antagonistic to tumor immunotherapy. Contrary to conventional belief, recent studies have shown that combining chemotherapy with immunotherapy resulted in enhanced anti-tumor immunity and improved therapeutic outcome. The mechanisms by which the use of chemotherapy paradoxically benefits immunotherapy await elucidation. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are a lymphocyte subset which plays a crucial role in inhibiting tumor-reactive effector cell functions and suppressing anti-tumor immunity. We hypothesize that chemotherapy benefits immunotherapy by preferentially impairing Treg, in effect eliminating immunosuppressive elements and augmenting the immune function of anti-tumor effector cells. Clarification of how chemotherapy exerts its immunomodulatory effects will aid in the development of better combination strategies of chemoimmunotherapy in the treatment of cancer.     

微针介导的浅表肿瘤治疗研究进展

作为一种新兴的给药方式,微针透皮给药具有微创无痛、安全高效、使用方便及改善患者依从性等优点.在浅表肿瘤治疗中,微针可以有效刺穿皮肤角质层,将负载的药物高效传递并富集于肿瘤部位,从而避免肝脏首过效应,防止胃肠道副作用,可极大地提高药物的利用率.在相同剂量下,相对于静脉注射给药及肿瘤内注射给药,微针透皮给药表现出更好的治疗...     

Tumor microenvironment: hypoxia and buffer capacity for immunotherapy

In recent years, significant progress has been made in the study of tumor biology and anti-tumor immunotherapy. However, the cellular and molecular mechanisms of tumor progression still remain obscure. As we know, tumor microenvironment that can directly influence tumor development and prognosis has attracted much attention of large number of immunologists. Accumulated evidence has suggested that tumor microenvironment is in a hypoxic condition, under which immune cells may exhibit distinct functions compared to those under normal oxygen tension. The article we propose here will offer a novel point of view for understanding tumor microenvironment in order to instruct clinical immunotherapy. Just like the pH buffer system in human body, interactions of immune cells in tumor microenvironment may also constitute a buffer system, the balance of which is of great importance during immunotherapy for tumors. However, many protocols for tumor immunotherapy in clinic at present have not taken it into account, so the therapeutic outcome is often disappointing. In the present study, we have demonstrated the effect of Corynebacterium parvum, a well known immune stimulator, on malignant melanoma. Cell ingredients in tumor-infiltrating lymphocytes (TIL) and their anti-tumor effect have been altered when dosage of Corynebacterium parvum is changed. So, to obtain better therapeutic purposes, what we should do first is to detect an index to evaluate immune buffer capacity for the patient during tumor immunotherapy, then to choose appropriate drug doses to augment buffer capacity for their immune buffer system. Taken together, the hypothesis proposed here may help understand the pathogenesis of tumor progression and design more effective strategy for clinical immunotherapy for tumors.     

Promising approaches in cancer immunotherapy

Immunotherapy is a promising field, which enhances and harnesses the powers of the host immune system against cancer and in recent years, has become a major application of the fundamental research of cancer immunology. Cancer immunotherapy is often more targeted than non-specific therapy approaches, including radiotherapy or chemotherapy, as the immune system can be trained to remember cancer cells, highlighting a durable approach that can be maintained after the treatment completion. Immunotherapy functions by directing the immune system to attack the tumour cells via targeting tumour antigens, also enhancing the existing anti-tumour immune responses. Current strategies include non-specific immunotherapy, cancer vaccines, oncolytic virus therapy, monoclonal antibodies, immune checkpoints and T cell therapy. The combination of effective approaches can increase the immunotherapy efficacy, leading to durable anti-tumour immune responses. This review will discuss the immunotherapy approaches, particularly immune checkpoints and T cell therapy, which are the most common clinical applications in cancer immunotherapy.     

The immunological consequences of photodynamic treatment of cancer,a literature review

In this review we discuss the effect of photodynamic treatment (PDT) of solid tumors on the immune response. The effect on both the innate and adapted immune response is discussed. We have summarized the evidence that PDT causes or enhances an anti-tumor response. PDT is a local treatment in which the treated tumor remains in situ while the immune system is only locally affected and still functional in contrast with e.g. after systemic chemotherapy. We conclude that PDT of cancer is a way of in situ vaccination to induce a systemic antitumor response. In general, immune cells are found in the tumor stroma, separated from tumor cells by extracellular matrix and basal membrane-like structures. We hypothesize that PDT destroys the structure of a tumor, thereby enabling direct interaction between immune cells and tumor cells resulting in the systemic anti-tumor immune response.     

肝癌靶向载体药物的靶向作用与应用分析

背景：肝癌是常见的恶性肿瘤之一,选择有效的治疗药物及治疗方法具有重要的意义。 目的：评价载体缓释化疗药物对肝癌的靶向治疗作用及效果。 方法：分析临床常用的肝癌化疗药物5-氟尿嘧啶、丝裂霉素以及表阿霉素载体缓释系统对肝脏肿瘤的靶向性特征以及对肿瘤的抑制和杀伤作用。并观察总结海南省农垦总医院肿瘤内科163例中晚期肝癌患者应用化疗药物5-氟尿嘧啶、丝裂霉素、表阿霉素,同时采用导管动脉化疗栓塞辅助治疗的临床效果。 结果与结论：5-氟尿嘧啶、丝裂霉素以及表阿霉素载体缓释系统通过不同的作用机制显示出对肝脏肿瘤的靶向性特征,并且对肝脏肿瘤具有较高的抑制和杀伤作用,减少药物用量,降低毒副作用,提高治疗效果。此外,治疗时辅助应用导管动脉化疗栓塞可以延长患者的生存期,提高肝癌的治疗效果。     

Active Immunotherapy of Cancer

Clinical progress in the field of cancer immunotherapy has been slow for many years but within the last 5 years, breakthrough successes have brought immunotherapy to the forefront in cancer therapy. Promising results have been observed in a variety of cancers including solid tumors and hematological malignancies with adoptive cell therapy using natural host tumor infiltrating lymphocytes, host cells that have been genetically engineered with antitumor T-cell receptors or chimeric antigen receptors, immune checkpoint inhibitors like anti-CTLA-4, anti-PD-1 or PD-L1 monoclonal antibodies and oncolytic virus-based immunotherapy. However, most treatment modalities have shown limited efficacy with single therapy. The complex nature of cancer with intra- and inter-tumor antigen and genomic heterogeneity coupled with the immune suppressive microenvironment emphasizes the prospect of personalized targeted immunotherapy to manipulate the patient’s own immune system against cancer. For successful, robust and long-lasting cure of cancer, a multi-modal approach is essential, combining anti-tumor cell therapy with manipulation of multiple pathways in the tumor microenvironment to ameliorate tumor-induced immunosuppression.     

NK cell-based immunotherapy for cancer

Natural killer (NK) cells can induce an antigen-independent immune response against malignant cells. A growing number of scientific reports and clinical studies have shown promising anti-tumor effects when using NK cell-based immunotherapy. Currently, various approaches are being used to enhance the number and function of NK cells. One approach uses cytokines to selectively boost both the number as well as the efficacy of anti-tumor functions of NK cells. Another emerging approach focuses on checkpoint inhibitors targeting the NK cell receptor. Furthermore, bi-specific and tri-specific engagers have been developed to enhance the specific immune response by cross-linking specific tumor antigens to effector cells. In addition, NK cell adoptive transfer therapies have shown promising prospects. Among the various sources of adoptive transfer NK cells, allogeneic haploidentical NK cells that have undergone short- or long-term activation or expansion have also demonstrated effective anti-tumor effects with a low rate of rejection and side effects. CAR-NKs, derived from a new type of genetic modification, show enhanced NK cell cytotoxicity, specificity, and targeting. These NK cell-based therapies have exhibited promising results in clinical trials with malignant tumors. In this review, the current progress on NK cell-based therapeutic approaches, NK cell manufacturing techniques and tumor therapy outcomes are discussed.