First mechanism: there is a link and triple coincidence of fas receptor (D95) in the surface of target cells by presence of Fas-ligand (or CD 95L) in the surface of immune ells (Fas-Fas L includes TNF and TNF family member such as CD27L, CD39L and CD40L.. Fas L system induces apoptosis and prevents apopyosis. The second mechanism: the phenomenon of cell dissolution due to activity of granule of cytotoxic T lymphocyte (CTL) out cell (granule exocytosis).
T-Lymphocytes, Cytotoxic ; Defense Mechanisms

Humans ; T-Lymphocytes, Cytotoxic ; immunology ; virology

OBJECTIVETo study the feasibility of dendritic cells (DCs) vaccine on the therapy of tongue carcinoma and find the better way of antigen load.

METHODSThe antigen peptides of Tca8113 cells were obtained by acid eluted technique and repetitive freeze thaw method. Separating T cell and inducing dendritic cells were obtained from human peripheral blood monocyte. Divided into three groups: Weak acid elution method antigen group, anti-freeze-thaw method antigen group, and the control group (without tumor antigen). T cells and UCs were mixed to culture by different effector-target ratio. Using MTT assay measured the quantities of absorbance and calculated stimulation index. Dendrtic cells pulsed with antigen were mixed with T cells by different effector-target ratio. MIT assay was used to measure the quantities of absorbance and calculate killing rate.

RESULTSDCs vaccine was constructed successfully. DCs vaccine can induce T lymphocytes to kill Tca8113 cells and display the dose-effect relationship. There was significant difference among the three groups. The acid eluted and repetitive freeze thaw groups were better than the control group. The acid eluted group was better than repetitive freeze thaw group.

CONCLUSIONDCs vaccine can induce T lymphocytes to kill Tca8113 cells. The antigen peptides obtained by acid eluted technique is better than repetitive freeze thaw method in immunotherapy of tongue cancer.

Despite the chemotherapy is successful in inducing remission of hematologic malignancy, this disease also has a high probability of relapse; besides, the toxicity of chemotherapy for these patients can not be avoided. Researchers have been attempting to eliminate tumor cells by immunotherapy. Recently, various leukemia-associated antigens (LAA) that are recognized by cytotoxic T cell (CTL) in the context of HLA class I molecules have been identified. These LAA include WT1, PR-3, RHAMM, BCR-ABL and Aur-A. On the basis of these findings, various clinical trials of immunotherapy for hematologic malignancy including tumor peptide vaccination, adoptive T cell therapy, NK cell therapy and dendritic cells-cytokine induced killer (DC-CIK) cell therapy are on going. In this review, the current status and future feasibility of cellular immunotherapy for leukemia are discussed.
Humans ; Immunotherapy, Adoptive ; Leukemia ; therapy ; T-Lymphocytes, Cytotoxic ; immunology

Veto activity was defined as the capacity of specifically downregulating cytotoxic T-precursor cell (CTL-p) directed against antigens of the veto cells themselves but not against third-party antigens. Many studies have shown that the most potent veto cells are CD8(+) cytotoxic T lymphocytes (CD8(+)CTLs). Effectively, CD8(+)CTLs of donor origin can facilitate engraftment of donor's stem cells by eliminating host-alloreactive T lymphocytes. In this article, effect mechanisms, depletion of GVH ex vivo, application in vivo, synergistic enhancement with rapamycin and regulatory T cells, and anti-tumor effect in the hematopoietic stem cell transplantation are summarized.
Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; T-Lymphocytes, Cytotoxic

OBJECTIVETo study the influence of thermochemotherapy on the activity of cytotoxic T lymphocyte (CTL) in peripheral blood of patients with oral maxillofacial cancer.

METHODSTwenty-one subjects with oral maxillofacial cancer were treated by thermochemotherapy, and the activity of CTL in peripheral blood was analyzed.

RESULTSThermochemotherapy can obviously enhance the activity of CTL (P<0.01).

CONCLUSIONThermochemotherapy can enhance the activity of CTL, thus enhance the patient's immune function. Therefore, it can enhance the antitumor response in whole body.

PURPOSE: Mouse liver nonparenchymal cells play an important role in the development of active apoptosis in graft- infiltrating cytotoxic T lymphocytes, and this apoptosis can be an explanation for liver graft acceptance. We intended to clarify whether immature mouse liver dendritic cells can induce apoptosis in allogeneic activated T cells and determine which mechanism is involved in this phenomenon. METHODS: A radiometric DNA fragmentation test ("JAM" assay) was used to determine whether mouse liver dendritic cells were able to induce activated T-cell apoptosis in vitro. In addition, immunohistochemical staining for Bax and Bcl-2 was examined to clarify whether Bax or Bcl-2 was involved in this apoptosis. RESULTS: Immature mouse liver dendritic cells were quite strong inducers of activated T cell apoptotic death in allogeneic mice in vitro (39.2+/-13.2% at E/T ratio=12.5/1) compared with spleen cells as effectors (4.7+/-13.4% at E/T ratio=12.5/1) (P<0.0001). By using immunohistochemical staining, we also showed that Bax might play some role in this phenonenon, but that Bcl-2 might not. CONCLUSION: Our data indicate that immature mouse liver dendritic cells might have a strong apoptotic activity toward activated T cells in allogeneic mice in vitro through a Bax-involved mechanism.
Animals ; Apoptosis* ; Dendritic Cells* ; DNA Fragmentation ; Liver* ; Mice* ; Spleen ; T-Lymphocytes* ; T-Lymphocytes, Cytotoxic ; Transplants

Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4+ T cells and CD8+ cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.
Dendritic Cells ; Humans ; Immunotherapy ; Multiple Myeloma ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Tumor Microenvironment ; Vaccination

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study, whether changes in tumor infiltrating lymphocytes take place after neoadjuvant chemotherapy, and if these correlate with the response to treatment in breast cancer were analyzed. METHODS: Neoadjuvant chemotherapy (Adriamycin: 50 mg/m2 +docetaxel: 75 mg/m2, q3wks, 3 treatments) was followed by definitive surgical management. Histological sections from the pre-treatment core-needle biopsy and post-treatment surgical specimens of 17 patients were analyzed for the extent of lymphocytes infiltration. Infiltrated lymphocytes have been recognized as tumor-infiltrating lymphocytes (TILs; lymphocytes present within tumor cell nests). The modified Black's scoring system was used for grading the extent of lymphocytes infiltration, with immunohistochemical (IHC) staining used to characterize the TILs. RESULTS: Pre-treatment lymphocytic infiltrates within the tumor were minimal in the majority of patients, and showed no relationship with the response. A marked increase of TILs after chemotherapeutic treatment was noted in patients according to the following response; complete response: 4/4 (100%), partial response: 2/6 (33.3%), stable disease: 0/7 (0%) (P=0.004). Histological sections stained with IHC staining revealed the increased TILs were CD8 positive cytotoxic T-lymphocytes. CONCLUSION: These results suggest that the development of TILs after treatment correlate with the response to neoadjuvant chemotherapy. Despite the limitation of this preliminary study, the extent of TILs change might be used as a predictor for the therapeutic efficacy of neoadjuvant chemotherapy in breast cancer.
Biological Factors ; Biopsy ; Breast Neoplasms* ; Breast* ; Drug Therapy* ; Humans ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating* ; T-Lymphocytes, Cytotoxic

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.
Adoptive Transfer ; Animals ; Antibodies, Blocking ; Autoimmunity ; Cell- and Tissue-Based Therapy ; Humans ; Lymphocytes ; Mice ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic* ; Zidovudine