We have shown that tumor-infiltrating lymphocyte (TIL) cultured in interleukin-2 (IL-2) acquired a potent antitumor activity and had target cell specificity.TIL exhibited higher cytotoxicity to autologous tumor cells than that of LAK cells grown under identical conditions (P0.05), so that it is possible to treat recurrent and unresectable tumor using TIL periodically.

It was demonstrated that TILs exhibited higher cytotoxicity to autologous tumor cells than that of LAK cells grown under identical conditions, and TILs had target cell specificity.The cytotoxicity of TILs to other tumor cells was lower than that of LAK cells, and TILs had no cytotoxicity to ConA-induced lymphoblast cells but LAK cells did have some cytotoxicity to the normal cells. The cytotoxicity of TILs to B 16 melanoma cells was reduced by monoclonal antimelanoma antibodies (M2590 and M562) which can block the activity of antimelanoma CTL, suggesting TILs contained high level of CTL activity. TILs were found to be more effective in their therapeutic potency in vivo on a percell basis than were LAK cells. These results indicate that TILs are more suitable to the adoptive immunotherapy of turn or as effector cells than LAK cells.

Although TNF alone was not capable of inducing LAK activity and could not enhance the LAK activity induced by IL-2 at optimal concentration (1000U/ml), TNF (500U/ml) was found to act synergistically with IL-2 at suboptimal concentration (10～100U/ml). This TNF/IL-2 synergistic effect was blocked by anti-TNF McAb (Z8) or anti-IL-2R? chain McAb (TU27). When TNF and IL-2/LAK cells were combined to treat tumor-bearing mice,TNF could potentiate significantly the therapeutic effect of IL-2/LAK cells in vivo.

In the present study,we have established an experimental model of human IL-6 gene thera-py with fibroblasts as cellular delivery and then observed its in vivo IL-6 level at different time.650-bp-long hIL-6 eDNA was inserted into Xho Ⅰ site of expression vector BCMGNeo carryingNeo~R gene and the resulting recombinant expression vector BCMGNeo-IL-6 was identified by re-striction enzyme digestion.BCMGNeo-IL-6 was transfected into NIH3T3 fibroblast cells by cal-cium phosphate coprecipitation method.A fibroblast cell clone secreting IL-6 activity in the cul-ture supernatants,and then analysed by Southern blot.The cell clone was expanded in vitro,en-capsulated into collagen and implanted i.p.into mice.Serum IL-6 could be detected even after15 days implantation.These results demonstrated that fibroblast cells could mediate in vivotransfer and efficient expression of hIL-6 gene,suggesting that this kind of gene therapy is reli-able.

Myeloid-derived suppressor cells(MDSCs) are heterogeneous cells derived from myeloid progenitor cells and immature myeloid cells(IMCs) in bone marrow;they are the progenitors of dendritic cells(DCs),macrophages and granulocytes.MDSCs proliferate in the blood,spleen,and tumor tissues in tumor-bearing mice and in the peripheral blood and tumor tissues in patients with cancer.MDSCs prevent tumors from attacks by body immunosurveillance and promote tumors progression through inhibiting both innate and adaptive antitumor immunity by a variety of pathways;they are recruited to the peripheral tissues from bone marrow and exert their inhibitory effects on antitumor immunity after activation in peripheral tissues.Chronic inflammation-related cytokines produced by tumors play crucial roles in the recruitment and activation of MDSCs.Progress has been made in antitumor therapies targeting MDSCs.But it has only been 10 years since the discovery of MDSCs,and many questions remain to be answered through experimental and clinical investigations.This review focuses on progress in MDSCs and its subsets,the recruitment and activation of MDSCs,the mechanisms of MDSCs-mediated immunosurveillance and antitumor treatment targeting MDSCs.

The outcome of current cancer therapy is far from satisfactory despite the considerable advancements have been achievedin life science and medicine.When looking for more potent drugs or technologies for cancer therapeutics,we shouht re-evaluate ourtraditional perception of caneer and have introspection whether we have some misunderstandings of cancer biology and the relationshipbetween cancer and host.In this commentary,the authors outlined their conceptual consideration of cancer,and proposed theirviewpoints about challenges and opportunities for cancer biotherapy.

Objective To investigate the effects of copper and zinc on the activity of cytochrome oxidase(COX)in neurons of rats and go further into the effect on energy metabolism of neurons.Methods After separate culturing of primary neurons and glial cells of the cortex of postnatal rats,neurons were treated with cupric sulphate at0,0.05,0.16,0.5mmol /L,zinc acetate at0,0.05,0.16,0.5mmol /L independently,and copper-zinc3?3pattern.Activi-ty of cytochrome oxidase was assessed with cytochemical method and imaging quantitative analysis.Results When neurons were treated with cupric sulphate at0.16?0.5mmol /L independently,COX activities in experimental groups significantly decreased compared with that in the control group,but there was no significant difference between the other groups treated with cupric sulphate or zinc acetate and the control group.When neurons were treated with copper com-bined with zinc,interaction on activity of COX showed no significance.Conclusion Copper could down-regulate and damage the activity of COX significanty,which was the most crucial energy metabolism enzyme,but combinning expo-sure of copper and zinc did not show significant interaction at the used levels.

DNA, as the material basis of all living cells, triggers innate immune responses through TLR9 and other cytosolic recognition receptors. In recent years, the research progress of TLR9 is mainly manifested by the following four aspects: (1) the determinants of TLR9 interacting with its ligands; (2) the mechanisms and the importance of TLR9 translocation from the endoplasmic reticulum to the endosome; (3) the roles of the endosomal acidification and maturation, and subsequent TLR9 cleavage in TLR9 signal transduction pathway; and (4) the possible mechanisms by which the organism distinguish self DNA from microbial DNA. Meanwhile, a series of experiments on TLR9 antagonists and TLR9 deficient mice confirmed the presence of TLR9-independent cytosolic DNA sensors. So far, three TLR9-independent DNA sensors have been found, and they are DAI, AIM2, and RNA polymerase Ⅲ.

There are multiple types of inhibitory immune cells in tumor. Among these cells, Treg (regulatory T cell) plays an extremely important role in tumor development and progression. Treg exihibits potent inhibitory effects on effector cells by a variety of mechanisms, which might be the the key factor for tumor immune escape. These mechanisms include inhibiting the effector cell function by inhibitory cytokines, killing effector cells by granzyme and profrin, interfering effector cell metabolism, and affecting Treg differentiation and proliferation by regulating the function of dendrtic cells, etc. The research on Treg has provided new strategies for tumor immunotherapy. Tumor immunotherapies targeting Treg and related immunosuppressive factors, such as deleting Treg nonsepcificlly or sepcificlly controling the numbers and functions of Treg, might have a bright future in clinical application.keyword regulatory T cell(Treg); neoplasms; immune escape; immunotherapy

Objective To investigate the effect of low intensity microwave electromagnetic fields (EMF) on energy metabolism of cerebral cortical neurons of postnatal rats. Methods The cultured neurons were exposed to low intensity 900 MHz continuous microwave EMF (SAR=0.38-3.22 mW/g) 2 hours a day for 4 to 6 consecutive days. The activity of cytochrome oxidase(CCO) was taken as the index for energy metabolism level. Results The results of cytochemistry showed that compared to the sham-exposed, a significant decrease of cytochrome oxidase activity in exposed neurons(0.38-3.22 mW/g P