Vaccines using dendritic cells,differentiated with propofol,enhance antitumor immunity in mice

Dendritic cell-based vaccines are useful for enhancing antitumor immunity. It has been suggested that propofol, an intravenous anesthetic, can enhance antitumor immunity in mice. We tested vaccine efficacy for eliciting antitumor immunity, using dendritic cells differentiated from bone marrow cells in the presence of propofol. Propofol-differentiated (but not control vehicle-differentiated) dendritic cells significantly delayed the growth of B16 melanoma in vivo. In vitro cytotoxic T cell activity was not affected by propofol. However, natural killer cell activity in mice vaccinated with dendritic cells differentiated in propofol was significantly upregulated, compared to unvaccinated mice.     

Enhancement of antitumor immunity by thymosin in hypocorticalism

Bilateral adrenalectomy and administration of thymosin (fraction 3) after adrenalectomy inhibit to different degrees the development of mammary gland tumors induced in rats by 7,12-dimethylbenzanthracene. The maximal effect was observed from the use of thymosin in conjunction with hypocorticalism; there was a substantial reduction in the frequency of developing neoplasms, the latent period of their development was lengthened, and their growth retarded.Kiev Roentgeno-Radiologic and Oncologic Research Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR L. I. Medved'.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 192–194, August, 1979.     

热处理淋巴瘤细胞增强树突状细胞介导的抗瘤效应研究

目的:探讨淋巴瘤细胞热处理后作为抗原,冲击树突状细胞而引发的抗淋巴瘤免疫效应。方法:用健康人外周血分离出单核细胞,体外培养树突状细胞(Dendritic cells,DCs),将淋巴瘤细胞株热处理(42℃,2小时)培养24小时后负载于DCs,在流式细胞仪上检测DCs的免疫表型变化;负载抗原后的DCs与淋巴细胞混合反应,以MTT法评价细胞毒性及在流式细胞仪上检测淋巴细胞的免疫表型;ELISPOT法检测细胞内因子IFNγ-的释放。结果:在两实验组中,DCs负载了热处理的淋巴瘤抗原后,细胞表面的共刺激分子和MHCⅡ类分子表达水平较对照组明显增加(P0.05),而两组之间差别无显著性(P0.05);经热处理的肿瘤细胞负载于DCs后,与淋巴细胞混合后IFNγ-的释放量明显增加;混合淋巴细胞反应后,细胞毒性实验(MTT法)和流式细胞仪检测结果均显示两实验组的杀瘤作用强于对照组(P0.05),两组之间无显著差别(P0.05)。结论:用热处理的淋巴瘤细胞作为肿瘤抗原冲击DC,能够增强抗淋巴瘤效应。     

Effect of subhypnotic doses of dexmedetomidine on antitumor immunity in mice

Dexmedetomidine, a selective alpha2 adrenergic receptor agonist, is a drug often used for sedation. Despite the high prevalence of sedating patients with tumors in intensive care settings, little is known about the effect of sedative drugs on tumor growth. We studied the effect of dexmedetomidine on antitumor immunity in mice. Subhypnotic doses of dexmedetomidine decreased interleukin (IL)-12 production from thioglycollate-induced macrophages. The treatment also decreased the ratio of the helper T lymphocytes subsets, Th1 to Th2 (Th1/Th2), in the spleen. Following subcutaneous inoculation of EL4 T-cell lymphoma cells, dexmedetomidine further decreased the splenic Th1/Th2 ratio and activity of EL4-specific cytotoxic T lymphocytes (CTLs). Finally, treatment with dexmedetomidine accelerated EL4 growth in mice. These data show that treatment of mice with subhypnotic doses of dexmedetomidine down-regulates antitumor immunity, possibly through the decreased production of IL-12 from antigen presenting cells, resulting in a Th2 shift and decreased CTL activity against EL4 in mice.     

模拟失重抑制荷黑素瘤小鼠的T淋巴细胞抗肿瘤免疫功能

目的 研究模拟失重对小鼠T淋巴细胞抗肿瘤免疫功能的影响.方法 小鼠右后肢皮下注射B16细胞建立移植性恶性黑素瘤模型,采用头低位-15°～20°尾吊小鼠模拟失重模型.观察模拟失重对荷瘤小鼠肿瘤体积和生存时间的影响;采用全自动血细胞分析仪和流式细胞仪分别检测模拟失重条件下荷瘤小鼠外周血白细胞、淋巴细胞的变化和T淋巴细胞亚群的变化;采用ELISA法和LDH释放法分别检测模拟失重对肿瘤细胞诱导T淋巴细胞产生IL-2、TNF-α、IFN-γ的水平和肿瘤特异性CTL对肿瘤细胞杀伤活性的影响.结果 与对照组相比,模拟失重组荷瘤小鼠肿瘤生长速度加快,生存期缩短,外周血淋巴细胞总数降低,淋巴细胞比例降低,CD3+、CD4 +/CD3+、CD8+/CD3+T淋巴细胞所占比例降低,丝裂原诱导的脾脏T淋巴细胞增殖能力降低(P＜0.05或P＜0.01).模拟失重条件下,肿瘤细胞诱导产生的细胞因子IL-2、IFN-γ和TNF-α水平降低,肿瘤特异性CTL对肿瘤细胞的杀伤活性降低(P＜0.05或P＜0.01).结论 模拟失重抑制小鼠T淋巴细胞抗肿瘤免疫功能.     

Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer

Cancer vaccines using dendritic cells (DCs) have been shown to induce antitumor immunity and have recently been applied to non-immunogenic cancers, such as pancreatic cancer. In this study, we utilized DCs loaded with heat-treated tumor lysate (HTL-DC) as a vaccine in order to stimulate antitumor immunity in a murine pancreatic cancer model and compared them to DCs loaded with tumor lysate (TL-DC). The poorly immunogenic mouse ductal pancreatic cancer cell line PANC02 with syngeneic mouse strain C57BL/6 was used as a model. Inducible heat shock proteins (HSPs) were significantly increased in HTL (HSP70 and HSP90). Tumor size measurements indicated that HTL-DC induced stronger tumor suppression than unpulsed DC or TL-DC (43% reduction in tumor volume compared to control group). T cell proliferation assay and IFN-gamma ELISPOT assay showed that T cell activation increased in the following order: DC相似文献   

Adenovirus-mediated CCL20/IL-15 gene transfer enhances antitumor immunity in mice

The CCL20 chemokine has potent antitumor activities through chemoattracting immature dentritic cells. But the maturation status of tumoral dentritic cells is important limiting factors in DC-based immunity. The endogenous availability of IL-15 was effective in inducing the dentritic cells maturation and IL-15 also shows tumor-specific antitumor activities. We constructed a CCL20/IL-15 bicistronic adenovirus (Ad-CCL20-IL-15) and confirmed its combined antitumor effect in vitro and in vivo. Intratumoral injection of Ad-CCL20-IL-15 into both CT-26 and B16F10 cells resulted in marked reduction of tumor growth in our model. Splenocytes treated by Ad-CCL20-IL-15 developed tumor-specific cytotoxic T cells and IFN-γ secretion could protect mice from rechallenging. This study suggests that CCL20/IL-15 can induce a strong antitumor immune response in tumor tissues and it is a suitable candidate for cancer immunotherapy.     

Mechanisms of specific and non-specific tumour immunity after azathioprine treatment of mice.

The ability of phagocyte-depleted spleen cells to lyse chicken erythrocytes (CRBC) in the presence of antibody was measured in mice which had been treated with the antimetabolite azathioprine. Single doses of the drug had no effect on this ability when measured on the day after administration. A 4-day course of 80 mg/kg/day of the drug markedly reduced splenic antibody-dependent cell-mediated cytotoxicity (ADCMC) although it reduced neither antibody responses nor the development of cytotoxic cells following subsequent immunization with an allogeneic tumour. Splenic phagocytosis and phagocyte-mediated ADCMC were both slightly enhanced following drug treatment. The implications of these findings are that the major antibody-dependent cytotoxic cell in phagocyte-depleted mouse spleen is normally in a state of proliferation, and plays no important role in antigen recognition.     

Gangliosides and antitumor immunity

Summary To elucidate the possible influence on the host's immune defense of ciruclating gangliosides released from tumor cells, the effects of exogeneous gangliosides on the activities of some lymphocyte subpopulations were examined. The mono- and disialyllactosylceramides GM3 and GD3, which frequently are present in elevated amounts in sera of tumor-bearing hosts, were found to inhibit strongly the cytotoxicity of natural killer cells, to stimulate T-suppressor activity of peripheral blood lymphocytes, and to inhibit their phytohemagglutinin-induced blast transformation. All these effects may be linked to the ability of gangliosides to modulate the arachidonic acid cascade in lymphoid cells, which for the first time was demonstrated in the course of our studies. Possible mechanisms underlying the immunomodulatory effects of serum gangliosides as well as their role in the escape of tumor cells from immune surveillance and inhibition of the hosts immune system are discussed.Abbreviations NK natural killer - Sph sphingosine - Cer ceramide - Neu neuraminic acid - 12-HETE 12-hydroxy-5,8,10,14-eicosatetraenoic acid - 12,20-diHETE 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid     

Rifampicin-induced suppression of antitumor immunity

The effect of rifampicin on transplantable tumor growth and antitumor immunity was studied. The growth of transplantable lung sarcoma was significantly enhanced in mice when rifampicin was given for 7 days or longer. Also, the antitumor effects of preimmunization of the animals with killed tumor cells were abrogated by this antibiotic.In vitro studies showed that spleen cells from tumor-bearing animals expressed significantly lower specific cytotoxicity toward syngeneic tumor cells, when the animals had been previously treated with rifampicin. Also, natural killer activity in healthy animals was diminished in mice receiving the antibiotic.Parts of this study have been presented at the 12^th International Congress of Chemotherapy, Florence, Italy, 1981     

Adoptive transfer of immunity toPlasmodium berghei after busulfan and cyclophosphamide treatment of recipient mice

Balb/c mice injected withP. berghei die about 21 days after infection. Successful cell transfer in mice was made possible by the pretreatment of the recipient with a combination of busulfan and cyclophosphamide. Cell counts showed that drug-treated mice contain 20 times less bone marrow cells than normal mice, and when injected withP. berghei die significantly later than normal controls. The animals were injected with normal (NBM) and immune bone marrow and normal (NSp) and immune spleen (ISp). The results obtained showed that ISp lengthens significantly the average survival time, producing cure of 50% of the recipients. Transfer of NSp and NBM also lengthens the average survival time.     

Icaritin promotes tumor T‐cell infiltration and induces antitumor immunity in mice

Icaritin, a hydrolytic product of icariin isolated from traditional Chinese herbal medicine genus Epimedium, has many pharmacological and biological activities. Here, we show that icaritin can effectively decrease tumor burden of murine B16F10 melanoma and MC38 colorectal tumors in a T‐cell dependent manner. The treatment effects are associated with increased CD8 T‐cell infiltration and increased effector memory T‐cell frequency. In vivo depletion of CD8 T cell using an anti‐CD8 monoclonal antibody abolished the antitumor effect, which supports the critical role of CD8 T cells during icaritin treatment. By analyzing immune cells in the tumor tissue, we found reduced frequency of CD11b⁺Gr1⁺ myeloid‐derived suppression cells (MDSCs) infiltration and downregulation of PD‐L1 expression on MDSCs after icaritin treatment. This was not limited to MDSCs, as icaritin also decreased the expression of PD‐L1 on neutrophils. Importantly, the combination of anti‐PD‐1/CTLA‐4 and icaritin significantly enhances antitumor ability and increases the efficacy of either treatment alone. Our findings reveal that icaritin induces antitumor immunity in a CD8 T‐cell‐dependent way and justify further investigation of combining immune checkpoint therapy to icaritin‐based antitumor therapy.     

Induction of antitumor acquired immunity by baculovirus Autographa californica multiple nuclear polyhedrosis virus infection in mice

The baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been studied as a gene therapy vector. Here, we demonstrated that AcMNPV induces antitumor acquired immunity. These results suggest that AcMNPV has the potential to be an efficient virus or tumor therapy agent which induces innate and acquired immunity.     

高渗盐水对手术伤口愈合的影响及其免疫机理的探讨

本研究比较了高渗盐水和生理盐水处理，对手术小鼠细胞免疫功能和伤口愈合的影响。结果表明，高渗盐水处理组小鼠腹壁切口裂开的张力（１４９．０±９．１ｍｍＨｇ）明显高于生理盐水处理组（１２４．１±９．２ｍｍＨｇ）；高渗盐水处理组的迟发型超敏反应（ＤＴＨ）程度（０．０７３ｇ±０．０２５ｇ）和淋巴细胞增殖能力（刺激指数１８．０±９．６）均明显高于生理盐水处理组（分别为０．０４５ｇ±０．００９ｇ和８．５±７．６）。体外实验还发现，提高培养液中氯化钠的浓度，术后２４ｈ淋巴细胞的活性增加，表明高渗盐水处理具有提高术后小鼠细胞免疫功能及促进伤口愈合的作用     

Transfusions of syngeneic blood do not seem to induce suppressive effect on antitumor or transplantation immunity in mice

There was no prolongation of allogeneic heart survival or acceleration of tumor development in mice pretransfused with syngeneic blood. Analogous transfusion of donor-specific (allogeneic) blood, without additional immunosuppression, resulted in prolongation of allogeneic heart survival. These results argue against participation of some immunologically unspecific mechanisms in immunosuppressive effect of blood transfusion on transplantation immunity in this model.