ABSTRACT
Pyroptosis is a type of programmed cell death distincted from apoptosis and necrosis, which is accompanied by the lysis of cell membranes and the release of cell contents. Pyroptosis occurs as mediated by Gasdermin protein family and is dependent on the activity of caspase. GSDME is one of the most important members of the Gasdermin protein superfamily. GSDME-mediated pyroptosis relies on the activity of caspase-3. In recent years, with further research on pyroptosis, the mechanism of GSDME-induced pyroptosis is becoming clear. Numerous studies have shown that GSDME-mediated pyroptosis plays an important role in the occurrence and development of tumors, as well as chemotherapy resistance. However, GSDME-mediated pyroptosis has no specificity and can induce pyroptosis of normal cells in the body while inducing tumor cell pyroptosis, thus causing different degrees of damage to various organs of the body. Further study on the mechanism of GSDME-induced pyroptosis, the role of GSDME in malignant tumors and the adverse reactions of chemotherapy can provide new ideas for tumor monitoring, treatment and prognosis judgment.
ABSTRACT
Gasdermin E is closely related to neoplasms, which is involved in the occurrence and development of neoplasms through gene methylation, gene mutation or other ways. Pyroptosis mediated by gasdermin E is involved in drug therapy of various neoplasms, which provides a new theoretical basis for drug therapy of neoplasms. The study of gasdermin E aims to deepen the understanding of neoplasms and provide a new perspective for the prevention and treatment of neoplasms.
ABSTRACT
Objective To explore immunotherapy effective combined with active immunotherapy in different time according rats bearing-tumor after paclitaxel and carboplatin chemotherapy, and to identify the optimization time and strategy of vaccine and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. Methods The dynamic immunocytes number and function in established tumor treated with paclitaxel and carboplatin chemotherapy were investigated. The changes of established tumor volume and immune function of different groups were observed according to combining different time after chemotherapy and vaccine. Results Lymphopenia was observed and the number of lymphocyte subset decreased remarkably on the 6th day, but all cells were found almost recovered on 15th day after chemotherapy. There is the process of immune-enhancing from post-chemotherapy 6 day to 10 day and reversal of immune suppression temporary. The combination post-chemotherapy 6 day with CTL caused a significantly delayed tumor growth in both tumor models and induced significant the proliferation of T lymphocyte by [H] 3 releasing. The number of CD8+T cell is the highest, but the expression of Tr cell was lowest in the group of post-chemotherapy 6 day with CTL. Furthermore, the ability of CD8+T secretion IFN-γ is the most in the post-chemotherapy 6 day with immunotherapy groups. Conclusion Combinational paclitaxel and carboplatin chemotherapy has synergistic effects with active immunotherapy boosting against tumor during window periods, where 6 days after chemotherapy with the most decreased number of lymphocytes in the animal periphery might represent the optimal checkpoint for the immune therapy against tumors. Therefore, monitoring the immune status of tumor patients might become one of the important prerequisites for the effective immune therapy when designing the comprehensive therapeutic strategies.
ABSTRACT
Objective: The purpose of this study is to investigate the dynamic changes in the numbers and functions of CD8~+T cells and NK cells in patients with advanced ovarian cancer undergoing first line chemotherapy,so as to identify whether there was a "window period" of anti-tumor immune suppression reverse after chemotherapy.Methods: Peripheral blood samples from each ovarian cancer patient were obtained before (S_0) and at day 5-7 (S_1),day 12-14 (S_2) and day 25-28 (S_3) after Chemotherapy in 13 patients.The numbers and proportions of CD3~+,CD4~+,CD8~+ and nature killer (NK) cells were analyzed by flow cytometry technique.The percentages of specific IFN-γ-secreting CD8~+ cells were also calculated after that peripheral lymphocytes had been stimulated with self tumor lysates.Cytotoxicity of NK cells against K562 cells was detected by LDH releasing assay.Results: The numbers of CD3~+,CD4~+,CD8~+T cells and NK cells reduced to the lowest on S1.Compared to those of the control group,and the percentages of IFN-γ-secreting CD8~+T cells were remarkably higher on S_1,S_2 and S_3 when CD8~+T cells were stimulated with autologous tumor antigen,and the percentage of CD8~+IFN-γ~+ cell reached the highest on S2.No significant differences of NK cell cytotoxicity against K562 cells were found on S_1,S_2 and S_3 compared to S0.Conclusion: Paclitaxel and carboplatin induce lymphopenia,which triggers the temporary immune reconstitution.During immune reconstitution the enhanced priming of CD8~+T cell response by autologons tumor antigen is found while the function of NK cells does not change significantly.It probably turns out that the" window period"during immune reconstitution offers a best opportunity for cancer immunotherapy.
ABSTRACT
Objective To investigate the changes of Tc1/Tc2 profiles and the cytotoxic function of CD8~+ cells in ovarian cancer patients undergoing paclitaxel and carboplatin chemotherapy, so as to identify whether there is a "window period" of anti-tumor immune suppression reverse after chemotherapy. Methods Blood samples from each ovarian cancer patient were obtained before (S_0) and at day 5-7 (S_1), day 12-14 (S_2) and day 25-28 (S_3) after chemotherapy in 13 patients. Thirteen age-matched healthy female volunteers were enrolled as a control group. Flow cytometry technique was employed to analyze the proportion of Tc1/Tc2. The numbers of specific IFN-γ, secreting CD8~+ cells were also calculated after peripheral lymphocytes had been stimulated with self tumor lysates. Results The proportion of Tel in CD8~+ cells increased re-markably on S2 while the proportion of Tc2 in CD8~+ cells remained no significant changes after chemothera-py. The ratio of Tc1 to Tc2 cells reached the highest on S_2. IFN-γ/secreting CD8~+ T cells also increased re-markably on S_2, especially when CD8~+ T cells were stimulated with autologous tumor antigen. Conclusion Paclitaxel and carboplatin induce the changes of Tc1/Tc2 profile and augment anti-tumor immune response by immune reconstitution. It probably turns out that the "window period" during immune reconstitution offers a best opportunity for cancer immunotherapy.
ABSTRACT
AIM: We investigated the numbers and proportions of lymphocyte subsets in advanced ovarian cancer patients undergoing chemotherapy, so as to identify whether there is immune reconstitution after chemotherapy, and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. METHODS: Blood samples from each ovarian cancer patient were obtained before (S_0) and at day 5-7 (S_1), day 12-14 (S_2) and day 25-28 (S_3) after chemotherapy in 13 patients. Flow cytometry technique was employed to analyse the numbers, proportions of CD3~+, CD4~+, CD8~+, CD4~+CD25~+ Treg and memory-like phenotype lymphocyte subsets. RESULTS: Lymphopenia was observed at S1 after chemotherapy, but lymphocytes were found gradually recovered after S1. The numbers of CD3~+, CD4~+, CD8~+T cells and CD4~+CD25~+ Treg cells reduced to the lowest on S_1. The proportions of CD8~+ T cells and CD4~+CD25~+ Treg cells reduced to the lowest on S_1 and S_2 respectively. The proportions of CD45RO~+ memory T cells increased significantly on S2 while the proportion of CD8~+CD45RA~+ T cells decreased remarkably on S_2. CONCLUSION: Paclitaxel and carboplatin induce lymphopenia at day 5-7 after chemotherapy, then comes the temporary immune reconstitution. It probably turns out that the window period during immune reconstitution offers a best opportunity for cancer immunotherapy.
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Objective:To explore whether apoptotic ovarian cancer cells induced by chemotherapy drugs paclitaxel and cisplatin can be cross-presented by dendritic cells(DCs) and enhance immune responses.Methods:DCs were induced from peripheral blood monocytes cells by GM-CSF/IL-4 for 6 d,then they were stimulated with either apoptotic ovarian cancer HO8910 cells,frozen-thawed HO8910 cells or control cells for 4 h.Their surface markers and phagocytotic ability were detected by flow cytometry and confocal microscopic scanning assay,respectively.DCs of different groups were cultured with CD8+ T cells isolated by magnetic cell sorting,and the ability of DCs to activate CD8+ T cells was evaluated by 3H-TdR,the activity of CTL to kill tumor cells was evaluated by LDH.Production of IFN-? by CD8+ T cells was measured by ELISPOT.Results:Apoptotic ovarian cancer cells induced by chemotherapy drugs paclitaxel and cisplatin could be phagocytized by DCs,which subsequently promoted the maturation and antigen presenting ability of DCs.Apoptotic ovarian cancer cells implused DCs significantly promoted proliferation of CD8+ T cells compared with that of control cells(P
ABSTRACT
Objective:The purpose of this study is to investigate the dynamic changes in the numbers and functions of CD8+T cells and NK cells in patients with advanced ovarian cancer undergoing first line chemotherapy,so as to identify whether there was a "window period" of anti-tumor immune suppression reverse after chemotherapy.Methods:Peripheral blood samples from each ovarian cancer patient were obtained before (S0) and at day 5-7 (S1),day 12-14 (S2) and day 25-28 (S3) after chemotherapy in 13 patients.The numbers and proportions of CD3+,CD4+,CD8+ and nature killer (NK) cells were analyzed by flow cytometry technique.The percentages of specific IFN-?-secreting CD8+cells were also calculated after that peripheral lymphocytes had been stimulated with self tumor lysates.Cytotoxicity of NK cells against K562 cells was detected by LDH releasing assay.Results:The numbers of CD3+,CD4+,CD8+T cells and NK cells reduced to the lowest on S1.Compared to those of the control group,and the percentages of IFN-?-secreting CD8+ T cells were remarkably higher on S1,S2 and S3 when CD8+ T cells were stimulated with autologous tumor antigen,and the percentage of CD8+ IFN-?+ cell reached the highest on S2.No significant differences of NK cell cytotoxicity against K562 cells were found on S1,S2 and S3 compared to S0.Conclusion:Paclitaxel and carboplatin induce lymphopenia,which triggers the temporary immune reconstitution.During immune reconstitution the enhanced priming of CD8+T cell response by autologous tumor antigen is found while the function of NK cells does not change significantly.It probably turns out that the "window period" during immune reconstitution offers a best opportunity for cancer immunotherapy.