Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells(DCs) and cytokine-induced killer cells(CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.AIM To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs,combined with different conventional treatments of HCC.METHODS We performed a literature search on PubMed and Web of Science up to February15, 2019. Long-term efficacy(overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.RESULTS A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio(RR) = 1.07;95%confidence interval(CI): 1.01-1.13, P = 0.02], 1 year(RR = 1.12;95%CI: 1.07-1.17, P< 0.00001), 3 years(RR = 1.23;95%CI: 1.15-1.31, P < 0.00001) and 5 years(RR =1.26;95%CI: 1.15-1.37, P < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo(RR = 0.50;95%CI: 0.36-0.69, P < 0.0001) and 1 year(RR = 0.82;95%CI: 0.75-0.89, P < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe,feasible treatment.CONCLUSION Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients’ prognosis by increasing overall survival and reducing cancer recurrence.

Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3-galactosyl epitope-ulsed dendritic cells and cytokine-induced killer cells

AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.

The Effect of Granulocyte Macrophage-Colony Stimulating Factor upon the Induction of Peripheral Blood Dendritic and Natural Killer Cells When Given Simultaneously with a Slow Continuous Doxorubicin Infusion

It has been demonstrated that it is safe to give Gm-Csf, together with Doxorubicin, by continuous intravenous infusion, thereby substantially increasing the amount of Doxorubicin administered to the average patient, and assuring that each patient receives an individually-determined safe and maximal amount of drug. It is known that Gm-Csf is a potent inducer of components that are major factors in an immunologic attack upon neoplasms. For that reason, we thought it would be worth evaluating in 4 patients’ surface markers of dendritic precursor cells, dendritic cells [DC], and natural killer [NK] cells during the infusion. While there was substantial variation in individual responses, all 4 patients receiving Gm-Csf developed persistent marked increases in cells with each of these markers. The significance of these findings will be discussed.

Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

Objective The aim of the present study was to investigate the effect of dendritic cell(DC)/cytokine-induced killer cell(CIK) immunobiological cancer therapy in patients with triple-negative breast cancer(TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrolled in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, differences between the two groups with regard to quality of life(Qo L), immunological indicators(CD3, CD4, CD8, and NK cell levels), disease-free survival(DFS), and side effects of chemotherapy and DC/CIK treatment were evaluated.Results In the DC/CIK group, the proportion of NK cells and CD3+ and CD4+ T-cell subgroups significantly increased, and the proportion of CD8+ cells decreased when they were compared before and after DC/CIK therapy(P < 0.05). However, there were no significant changes in the control group. By the final follow-up, DFS of the treatment group and the control group was 38.4 and 34.2 months, respectively. The Qo L improved in the patients treated with chemotherapy plus DC/CIK therapy compared with the patients treated with chemotherapy alone, and the difference between groups was significant(P < 0.05). The side effects of two groups were tolerable and not significantly different between the two groups.Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the control group, and was not associated with any obvious side effects. Therefore, DC/CIK therapy is a safe and effective method for the treatment of TNBC.

Gastric cancer-derived heat shock protein-gp96 peptide complex enhances dendritic cell activation

AIM To investigate the role of heat shock protein (HSP)glycoprotein (gp) 96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)2,5- diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha), respectively. Effect of cytotoxic T lymphocyte (CTL) on DCs incubated with HSP-gp96 was also evaluated by LDH release. All assays were performed in triplicate and the average values were reported. Comparison between groups was conducted using Student's t test. RESULTS T cells incubated with HSP-gp96 exhibited a marked increase in proliferation in a dose-dependent manner (P < 0.05). NK cell activity after gp96-GC peptide complex treatment was significantly higher than that after antigen peptide treatment (P < 0.05). The activity of CTLs incubated with DCs from three GC cells lines was obviously higher than that stimulated by GC antigen at ratios of 50: 1, 25: 1, 10: 1, and 5: 1 (P < 0.05). Furthermore, the secretion of TNF-alpha, IL-10, IL-12 (P70) and IFN-alpha markedly increased after incubation with HSP-gp96 (P < 0.05). CONCLUSION HSP-gp96 promotes T cell response, enhances DC antigen presentation and induces cytokine secretion, as well. HSP-gp96 has potential as immunotherapy for elimination of residual GC cells.

Inhibition effect of natural killer T cells on transplantation hepatocellular carcinoma in mice

Objective:The aim of this study was to investigate the inhibition effect of natural killer T(NKT) cells on transplantation hepatocellular carcinoma in mice.Methods:α-galactosylceramide(α-GalCer)-pulsed DC and Hep S were prepared as stimulus.Hepatoma xenograft model was established and mice were randomly divided into 4 groups(n=13 each group):(1) control group,intravenous injection of the same volume of saline.(2) mature DC group,intravenous injection of mature DC cells(4×106 cells).(3) α-GalCer-pulsed HepS group,intravenous injection of α-GalCer-pulsed HepS(4×106 cells).(4) α-GalCer-pulsed mature DC group,intravenous injection of α-GalCer-pulsed DC(4×106 cells).The changes of tumor volume in mice and survival period were measured every 2 days.Percentage of NKT cells in spleens and cytotoxicity of spleen cells were detected by flow cytometry.Tumor tissues were analyzed by histopathological examination.Results:In α-GalCer-pulsed Heps and DC groups,the average survival period was prolonged and tumor volume was markedly decreased,spleen cells and NKT cells were significantly increased,and tumor necrosis was evident,compared to the control group.Conclusion:α-GalCer-pulsed DC and HepS could activate NKT cells in vivo,also increase NKT cells cytotoxicity,inhibit the growth of hepatomas and prolong survival period.

Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARSCoV- 2 infection

Severe acute respiratory syndrome coronavirus-2 and the related coronavirus disease-19(COVID-19)is a worldwide emerging situation,which was initially reported in December 2019 in Wuhan,China.Currently,more than 7258842 new cases,and more than 411879 deaths have been reported globally.This new highly transmitted coronavirus is responsible for the development of severe acute respiratory distress syndrome.Due to this disorder,a great number of patients are hospitalized in the intensive care unit followed by connection to extracorporeal membrane oxygenation for breath supporting and survival.Severe acute respiratory distress syndrome is mostly accompanied by the secretion of proinflammatory cytokines,including interleukin(IL)-2,IL-6,IL-7,granulocyte colony-stimulating factor(GSCF),interferon-inducible protein 10(IP10),monocyte chemotactic protein-1(MCP1),macrophage inflammatory protein 1A(MIP1A),and tumor necrosis factor alpha(TNF-α),an event which is known as“cytokine storm”.Further disease pathology involves a generalized modulation of immune responses,leading to fatal multiorgan failure.Currently,no specific treatment or vaccination against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has been developed.Mesenchymal stromal cells(MSCs),which are known for their immunosuppressive actions,could be applied as an alternative co-therapy in critically-ill COVID-19 patients.Specifically,MSCs can regulate the immune responses through the conversion of Th1 to Th2,activation of M2 macrophages,and modulation of dendritic cells maturation.These key immunoregulatory properties of MSCs may be exerted either by produced soluble factors or by cell-cell contact interactions.To date,several clinical trials have been registered to assess the safety,efficacy,and therapeutic potential of MSCs in COVID-19.Moreover,MSC treatment may be effective for the reversion of ground-glass opacity of damaged lungs and reduce the tissue fibrosis.Taking into account the multifunctional properties of MSCs,the proposed stem-cell-based therapy may be proven significantly effective in critically-ill COVID-19 patients.The current therapeutic strategy may improve the patient’s overall condition and in parallel may decrease the mortality rate of the current disease.

Clinical study of co-treatment with DC-CIK cells for advanced solid carcinomas

Objective： The aim of this study was to observe the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid carcinoma patients. Methods： Isolated peripheral blood mononuclear cells （PBMCs） from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor （GM-CSF）, tumor necrosis factor-a （TNF-a） and interleukin-4 （IL-4） to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-y （IFN-y）, interleukin-2 （IL-2） and CD3 monoclonal antibody （CD3 McAb） to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results： Forty-two patients with measurable nidus, 2 achieved complete remission （CR）, 9 partial remission （PR） and 15 stable disease （SD）, while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion： DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.

The clinical effects of DC-CIK cells combined with chemotherapy in the treatment of advanced NSCLC

Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.

Multiple sclerosis and the role of immune cells

Multiple sclerosis(MS) is a complex disease with many different immune cells involved in its pathogenesis, and in particular T cells as the most recognized cell type. Recently, the innate immune system has also been researched for its effect on the disease. Hence, cells of the immune system play vital roles in either ameliorating or exacerbating the disease. The genetic and environmental factors, as well as the etiology and pathogenesis are of utmost importance for the development of MS. An insight into the roles play by T cells, B cells, natural killer cells, and dendritic cells in MS and the animal model experimental autoimmune encephalomyelitis, will be presented. Understanding the mechanisms of action for current therapeutic modalities should help developing new therapeutic tools to treat this disease and other autoimmune diseases.

Research on the biological activity and anti-tumor effect against lymphoma cells of DC-CIK cells

Objective： To investigate the proliferation capabilities, immunophenotype changes, level of secreted cytokines and activities against lymphoma cells under the condition that cytokine-induced killer （CIK） cells co-cultured with dendritic cells （DC） in vitro. Methods： DC and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by tapan-blue staining, killing activities were detected by MTT assay, immunophenotype changes were analyzed by flow cytometry, the IL-12 and INF-y levels of the cultured supernatants were detected by ELISA kits. Results： The proliferation capabilities of DC-CIK cells were significantly higher than that of CIK cells （P 〈 0.05）. Under the same condition, the ratio of double positive cells such as CD3^＋ CD8^＋, CD3^＋ CD56^＋ in CIK cells was significantly enhanced by co-cultured with DC cells （P 〈 0.05）. The level of IL-12 and INF-y secreted in supernatants was increased noticeably by co-cultured DC-CIK cells on day 3 compared to CIK cells which were cultured alone （P 〈 0.01 and P 〈 0.05）. Within the effector-target ratio range between 5：1 to 40：1, the activities against lymphoma cells of DC-CIK cells were much higher than that of CIK cells （P 〈 0.05）, and this effect was showed a positive correlation with the effector-target ratio. Conclusion： The proliferation capabilities, the level of secreted cytokines and the activities against lymphoma cells of DC-CIK cells were significantly higher than those of CIK cells. The research might provides theoretical and experimental basis for clinical immunotherapy of DC-CIK cells.

A randomized controlled trial of postoperative tumor lysate-pulsed dendritic cells and cytokine-induced killer cells immunotherapy in patients with localized and locally advanced renal cell carcinoma

Background It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma （RCC） after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate （TL）-pulsed dendritic cells （DCs） and cytokine-induced killer （CIK） cells in patients with localized or locally advanced RCC.

Liaison between natural killer cells and dendritic cells in human gestation

A successful pregnancy relies on immunological adaptations that allow the fetus to grow and develop in the uterus, despite being recognized by maternal immune cells. Among several immunocompetent cell types present within the human maternal/fetal interface, DC-SIGN~ dendritic cells （DCs） and CD56＋ natural killer （NK） cells are of major importance for early pregnancy maintenance, not only generating maternal immunological tolerance but also regulating stromal cell differentiation. Previous reports show the presence of NK-DC cell conjugates in first trimester human decidua, suggesting that these cells may play a role in the modulation of the local immune response within the uterus. While effective immunity is necessary to protect the mother from harmful pathogens, some form of tolerance must be activated to avoid an immune response against fetal antigens. This review article discusses current evidence concerning the functions of DC and NK cells in pregnancy and their liaison in human decidua.

Antitumour activities of cytokine-induced killer cells and dendritic cells in vitro and in vivo

Solid tumour cells show a resistance to immunological effector cells in vitro. The resistance may be one reason why these tumours withstand immunotherapeutic approaches in humans. Dendritic cells （DC） play an important role in the immune response to tumour associated antigens in humans. DC in the periphery capture and process antigens, express lymphocyte costimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune response.

Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy

Dendritic cell(DC)-based vaccines continue to be considered an attractive tool for cancer immunotherapy.DCs require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1(Th1)or Th2 responses.DCs play a role in natural killer(NK)cell activation,and NK cells are also able to activate and induce the maturation of DCs.We investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions occur.DCs that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce IL-12p70.NK cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte responses.Our data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses,which suggests that these cells may be useful for cancer immunotherapy.

免疫细胞及相关细胞因子在骨关节炎发病及治疗中的作用

背景:骨关节炎的发生发展与免疫异常密切相关,各种免疫细胞、免疫介质在骨关节炎发病过程中的重要性不断被阐明。目的:综述免疫细胞及相关细胞因子在骨关节炎发病及治疗中的作用,为今后骨关节炎的研究和防治提供新的思路。方法:以“骨关节炎,膝,巨噬细胞,T细胞,B细胞,自然杀伤细胞,树突状细胞,细胞因子,炎症因子,免疫细胞”“osteoarthritis,knee,macrophages,T cells,B cells,natural killer cells,dendritic cells,cytokines, inflammatory factors,immune cells”为检索词在中国知网、万方、维普和PubMed和Web of Science数据库中检索已发表的相关文献,阅读标题和摘要进行初筛,在阅读全文后,最后选取98篇文献进行综述。结果与结论:(1)既往研究认为骨关节炎发病与软骨磨损相关,近年来研究认为骨关节炎是免疫细胞广泛参与的一种慢性炎性状态,随着对骨关节炎发病机制的深入研究,学者们认为骨关节炎的发病机制是由早期先天免疫反应驱动的,这种免疫反应会逐步催化退行性变,最终导致关节微环境的改变。(2)各种免疫细胞和细胞因子是影响骨关节炎修复的关键因素,其中巨噬细胞、自然杀伤细胞参与滑膜炎症反应,T细胞免疫反应参与骨关节炎软骨的降解,并加重骨关节炎的病情。(3)免疫细胞分泌的白细胞介素1β、白细胞介素6、肿瘤坏死因子α、白细胞介素17和白细胞介素37等炎性细胞因子在骨关节炎的病理生理中发挥重要作用,其中白细胞介素1β是造成关节软骨破坏最重要的炎性因子。(4)在骨关节炎病早期阶段对免疫学危险因素进行评估,能够早期有效地进行治疗,可显著降低与骨关节炎相关的残疾、发病率和成本。(5)目前干细胞及其来源外泌体、生物材料进行免疫调节治疗骨关节炎的效果已在不同的实验模型中得到证实,但将其用于临床实践之前仍有大量的实验工作要做,随着新治疗靶点的发现,针对靶点进行相关治疗将为临床骨关节炎修复带来新的希望。

肿瘤特异性个体化多靶点DC-CIK治疗原发性肝癌的临床疗效与安全性

目的:评价肿瘤特异性个体化多靶点自体树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)治疗中晚期原发性肝癌(PLC)的临床疗效与安全性。方法:回顾性分析2019年10月至2021年9月东部战区总医院肿瘤科行DC-CIK治疗的119例中晚期PLC患者的临床资料。根据患者治疗时负载DC的抗原不同将患者分为两组,一组使用患者自体特异性多肽负载为pDC-CIK组(n=21),另一组使用肿瘤细胞裂解物负载为DC-CIK组(n=98)。分析两组患者治疗前后的临床资料,包括治疗效果和治疗前后甲胎蛋白、淋巴细胞亚群、细胞因子(IL-2、IFN-γ、TNF-α和IL-6)水平的变化、不良反应发生情况等。结果:119例PLC患者治疗后,pDC-CIK和DC-CIK组两组客观缓解率均为0%,疾病控制率分别为76.1%和72.4%(P>0.05)。治疗后两组患者CD3^(+)、CD4^(+)、CD8^(+)、CD56^(+)、CD25^(+)和CD4^(+)/CD8^(+)T淋巴细胞水平无统计学差异(均P>0.05),治疗后两组患者外周血IL-2、IFN-γ、TNF-α和IL-6的平均水平均显著高于治疗前(均P<0.001),两组患者治疗后外周血IL-2、TNF-α和IL-6的平均水平无显著差异(均P>0.05),而pDC-CIK组IFN-γ水平显著高于DC-CIK组(P<0.05)。pDC-CIK组患者平均生存时间为59.84个月,高于DC-CIK组的46.54个月,但无统计学差异(P=0.16)。治疗过程中无严重不良反应的发生。结论:PLC患者行肿瘤特异性个体化多靶点DC-CIK治疗是安全有效的,并能改善免疫功能,相较肿瘤细胞裂解物负载DC-CIK有进一步获益趋势。

肿瘤免疫编辑在黑素瘤肿瘤微环境中的研究进展

黑素瘤是人类癌症中免疫原性最强的肿瘤之一,对免疫治疗具有高度敏感性,因此免疫治疗已成为黑素瘤最具潜力的研究与应用领域。然而,与大多数肿瘤一样,黑素瘤通过各种途径获得抑制机制,并与人类免疫系统中各成分发生复杂的相互作用,使肿瘤细胞逃脱免疫系统的监视,最终导致黑素瘤的发展与转移。近几十年来,对黑素瘤相关形成细胞、免疫细胞及相关分子物质的深入研究取得了巨大进展,以此开发并批准几种免疫治疗药物,这些药物对部分晚期及转移性黑素瘤患者有益,但黑素瘤的免疫生物学研究仍然不足。本文从免疫编辑的角度回顾黑素瘤发生发展过程中免疫系统及相关细胞的演变过程,综述并整合黑素瘤特异性免疫方面的现有知识,以期在黑素瘤患者的治疗中有更广泛的应用,并寻找更有效的疗法。

DC联合CIK治疗156例局部晚期或晚期胰腺癌的临床疗效

目的:评价DC联合CIK治疗156例局部晚期或晚期胰腺癌的临床疗效。方法:回顾性分析2011年11月至2023年12月在东部战区总医院肿瘤科进行自体DC联合CIK治疗的156例局部晚期或晚期胰腺癌患者的临床资料。统计患者治疗前后血清肿瘤标志物、淋巴细胞亚群、细胞因子水平的变化、不良反应发生情况以及近期疗效、远期疗效。结果:156例胰腺癌患者中有92例治疗前后均进行了影像学检查,结果显示CR 0例,PR 0例,SD 42例,PD 50例,ORR为0%,DCR为45.65%。外周血CA199水平在治疗前后无显著差异,但有19例患者治疗后下降超过20%。治疗前后患者外周血CD3^(+)、CD4^(+)、CD8^(+)、CD56^(+)、CD25^(+)淋巴细胞亚群水平和CD4+/CD8+T细胞比值无统计学差异(P>0.05),治疗后患者外周血IL-2、IFN-γ的平均水平均显著高于治疗前(P<0.05),TNF-α和IL-6无显著差异(P>0.05)。156例患者mOS为8.53个月,1年累积生存率为39%,2年累积生存率为15%,3年累积生存率为15%,没有随访到5年的生存数据。治疗过程中未发生严重不良反应。结论:DC-CIK能使局部晚期和晚期胰腺癌患者产生抗肿瘤免疫反应,取得一定的客观疗效并可能使患者生存期延长。

DC-CIK不同输注方式治疗原发性肝癌的临床疗效和预后

目的:探讨不同途径输注DC-CIK对中晚期原发性肝癌(PLC)的治疗效果和预后价值。方法:回顾性分析2018年10月至2021年9月间东部战区总医院肿瘤科DC-CIK治疗的69例中晚期PLC患者的临床资料,根据DC-CIK治疗时采用的输注方式不同将患者分为肝动脉灌注(HAI)组(n=29)和静脉输注(Ⅳ)组(n=40),比较两组患者的临床疗效、外周血T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)T和CD4^(+)/CD8^(+)T细胞比值),以及细胞因子(IL-2、IL-6、IFN-γ和TNF-α)、甲胎蛋白(AFP)的变化、总生存期(OS)和不良反应发生情况。结果:69例PLC患者经DC-CIK治疗后,HAI组患者的客观缓解率(ORR)为0%,疾病控制率(DCR)为75.8%;Ⅳ组患者的ORR为0%,DCR为72.5%(P>0.05)。两组患者治疗前后T淋巴细胞亚群指标变化差异无统计学意义(均P>0.05),两组患者治疗后外周血IL-2、IL-6、IFN-γ和TNF-α的平均水平均显著高于治疗前(均P<0.01),两组间比较无显著差异(P>0.05);HAI组患者平均OS为48.17个月,Ⅳ组OS为39.65个月,两组间比较无显著差异(P>0.05)。治疗过程中无严重不良反应发生。结论:自体DC-CIK HAI治疗PLC安全有效,较Ⅳ治疗有提升临床获益的趋势,值得临床借鉴。