| Background: The immunological reasons of the tumor’s origin anddevelopment are as follows. Firstly, the changing of the specific molecules ontumor cell surface can reduce the body’s immune surveillance function andhelp to evade the body’s immune system monitoring. Secondly, cells inhibitthe activation of T cell epitope by not expressing MHCI antigen and otherantigen peptide. Lastly, Tumor cells help themselves to weaken the body’simmune rejection with secretion of immunosuppressive factors. Therefore, toimprove the immune function of organism is regarded as one of the importantmethods to prevent cancer, and can prolong the survival period of the cancerpatients.It has been made rapid progress since the first identification ofCD4+CD25+regulatory T cells (regulatory T cell, Treg) by Sckaguchi in1995.Researchers have found tumor cells in patient body can induce CD4+CD25+which plays a part in immune suppression and an important role inmaintaining the body’s immune balance and the inhibition of autoimmunereaction.CD4+CD25+Treg is divided into natural Treg and adaptive Treg. Thenatural Treg which develop from thymus T cells and grow to mature in themedulla of thymus, then transferred to the peripheral blood, are cell subsetswhich suppress autoimmune response. Adaptive Treg are cell subsets inducedfrom mature T cells under special Immune factors’ effects.CD4+CD25+Treg shows two characteristics on the function of immuneincompetent and immune suppression. CD4+CD25+Treg doesn’t respond tohigh concentration of interleukin2(IL-2) stimulation alone or/and T cellreceptor (TCR) stimulation as well as not secret IL-2. That is immune incompetent. Immune suppression is reflected in some mediated signal (suchas T cell receptor) stimulus to be activated, thereby inhibiting T cells (such asCD4+and CD8+) activation and proliferation, and inhibit non-specific antigen.CD4+CD25+Treg expresses a variety of cell surface molecules, such asCD25high, CTLA-4and GITR, and so on. At the same time, the CD4+CD25+Treg highly expresses Foxp3, so that Foxp3can be used as the characteristicmarker.Foxp3belongs to the fork wing shape helix transcription factor family. Itcontains the wings of the amino acid sequence of a conservative type spiraltranscription factor, and one C2H2zinc finger protein gene and a leucinezipper gene sequences. Human Foxp3gene locates in Xp11.23, it includingeleven coding exons, three non coding exons and ten introns, expressingmainly in the nucleus. The Foxp3gene is up-regulated proteins first, and it isthe precondition for enhanced development and achieves the best effect ofCD4+CD25+Treg cells.Numerous studies have shown that, in patients with lung cancer,esophageal cancer, breast cancer, gastrointestinal cancer, liver cancer andovarian cancer, the expression of CD4+CD25+Treg cells were found to havesignificantly increased in the peripheral blood or local tumor, suggesting thatCD4+CD25+Treg cells in the immune response of tumor play an importantrole.Pseudomonas Aeruginosa Injection, a kind of inactivation preparations, ismade for the expression of mannose sensitivity (PA-MSHA).PseudomonasAeruginosa Injection is formed through genetic engineering methods byPseudomonas aeruginosa as a carrier system. Research shows that, PA-MSHAcan make the structure and function of tumor cell membrane changes, thuschanging the biological behavior of tumor cells, decreasing tumor cellproliferation, invasion and metastasis, which activate the apoptotic processand the apoptosis of tumor cells. Many studies have shown that, PA-MSHAhas a strong immune stimulating activity. It can promote the production ofThl cytokines, and the activation of T cells, as well as stimulate cytotoxic T lymphocyte (CTL) generation,which enhances the specific cellular immunefunction of the organism. And it can indirectly promote the activation of NKcells so that enhance the nonspecific immune function. Clinical studies haveshown that PA-MSHA preparation can activate the body’s immune response,increase immune response level, rebuild the immune surveillance function, soas to restrain and kill cancer cells. At present, PA-MSHA has been broadlyused in adjuvant treatment of various malignancies.We will carry outPA-MSHA intervention on patients in the perioperation period, to study of theeffect on the immune function of postoperative patients with non-small celllung cancer and its safety evaluation.Methods: From Apr2013to Oct2013, the No.5department of medicalthoracic surgery of Hebei medical university fourth hospital, receive and curedto patients with NSCLC. All these patients were divided into the PseudomonasAcruginosa treatment (experimental group,30patients) and control group (30patients) according to the random number to the method (all subjects wereconfirmed by bronchoscopic findings and biopsy resents, all subjects neverhad the chemotherapy or radiotherapy before an operation). All subjects wereperformed standard radical operation for lung cancer. The patients in theexperimental group were injected PA-MSHA vaccine5ml into thoracic cavityat the end of surgery. On the1st,3rd,5th,7th and9th day, use PA-MSHA onetime in subcutaneous injection after the operation, one time1ml. The patientsin the control group were injected normal saline (NS)5ml into thoracic cavityat the end of surgery. On the1st,3rd,5th,7th and9th day, use NS one time insubcutaneous injection after the operation, one time1ml. Firstly, we proceedpreliminary experiment: the beginning of the ten patients admission to hospitalwere randomly divided into experimental group (five cases) and control group(five cases), all subjects were performed standard radical operation for lungcancer. The patients in the experimental group were injected PA-MSHAvaccine5ml into thoracic cavity at the end of surgery, on the1st,3rd,5th,7thand9th day, use PA-MSHA one time in subcutaneous injection after theoperation, one time1ml. The patients in the experimental group were injected PA-MSHA vaccine5ml into thoracic cavity at the end of surgery. On the1st,3rd,5th,7th and9th day, use PA-MSHA one time in subcutaneous injectionafter the operation, one time1ml. The patients in the control group wereinjected normal saline (NS)5ml into thoracic cavity at the end of surgery. Onthe1st,3rd,5th,7th and9th day, use NS one time in subcutaneous injectionafter the operation, one time1ml. From1d before surgery until12d after theoperation, all subjects from the two groups, used EDTA anticoagulant tubesseparately to collect peripheral venous blood samples2ml in order to test anumber of immunological indicators including the level of CD3+,CD4+,NK,CD4+CD25+regulatory T cell and Foxp3by flow cytometry within three hours.Analysis the immunological result of obvious change trend and find out thespecific time, respectively are the1st before surgery and the2nd,6th and10thafter the operation, these points in time are the best observation time of otherpatients. On the1st before surgery and the2nd,6th and10th after theoperation, the other patients from the two groups, used EDTA anticoagulanttubes separately to collect peripheral venous blood samples2ml in order totest a number of immunological indicators including the level ofCD3+,CD4+,NK, CD4+CD25+regulatory T cell and Foxp3by flow cytometrywithin three hours．At last, performed statistical analysis on all data by theSPSS19.0statistical analysis software.Results: The numbers of CD3+, CD4+and NK cells of two groups’patients were shown a trend of decline after rising first. Because surgical strikecould decline the immune function, leading to the temporary decline ofnumbers of CD3+, CD4+and NK cells in postoperative period. As gradualrecovery with body system function, the numbers of CD3+, CD4+and NKcells increased gradually, but the numbers of CD3+, CD4+and NK cells ofexperimental group on the10th day after the operation were significant higherthan the control group, explaining that PA-MSHA had positive regulatory rolefor the body cell function. The numbers of CD4+CD25+regulatory T cell andFoxp3cells of two groups after surgery were lower than those before surgery，and the numbers of CD4+CD25+regulatory T cell and Foxp3cells of experimental group on the2nd,6th and10th day after the operation weresignificant lower than those before surgery，while the numbers of CD4+CD25+regulatory T cell and Foxp3cells of control group on the10th day after theoperation were significant lower than those before surgery, explaining that thenumbers of CD4+CD25+regulatory T cell and foxp3cells of cancer patientsbefore surgery were higher. The values of CD4+CD25+regulatory T cell andfoxp3cells were reduced gradually after surgery, showing that CD4+CD25+regulatory T cell and Foxp3cells were playing an important role in non-smallcell lung cancer. The numbers of CD4+CD25+regulatory T cell and Foxp3cells in experimental group on the10th day after surgery were lower thanthose in control group, showing that PA-MSHA had negative regulationfunction for CD4+CD25+regulatory T cell and Foxp3in patients and alsoPA-MSHA promoted the reconstruction of immune function, and was moreconducive to enhance the immune function of postoperative patients.Conclusions: The immunologic function is low in the patients withNSCLC before an operation. Because of the surgical strike, the patients’immune function of all systems gets restored. The number of CD4+CD25+regulatory T cell and Foxp3are lower than the preoperative after the operationapparently in the patients were treated with PA-MSHA；These were a negativecorrelation between CD4+CD25+regulatory T cell the level of Foxp3cells andthe immune function organism. PA-MSHA can enhance the perioperativeperiod immunological status of patients with NSCLC and has satisfied safetyand tolerance for patients. |
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