Ratio Of NK Cells Research Articles

CX3CR1-dependent recruitment of mature NK cells into the central nervous system contributes to control autoimmune neuroinflammation.

Fractalkine receptor (CX3CR1)-deficient mice develop very severe experimental autoimmune encephalomyelitis (EAE), associated with impaired NK cell recruitment into the CNS. Yet, the precise implications of NK cells in autoimmune neuroinflammation remain elusive. Here, we investigated the pattern of NK cell mobilization and the contribution of CX3CR1 to NK cell dynamics in the EAE. We show that in both wild-type and CX3CR1-deficient EAE mice, NK cells are mobilized from the periphery and accumulate in the inflamed CNS. However, in CX3CR1-deficient mice, the infiltrated NK cells displayed an immature phenotype contrasting with the mature infiltrates in WT mice. This shift in the immature/mature CNS ratio contributes to EAE exacerbation in CX3CR1-deficient mice, since transfer of mature WT NK cells prior to immunization exerted a protective effect and normalized the CNS NK cell ratio. Moreover, mature CD11b(+) NK cells show higher degranulation in the presence of autoreactive 2D2 transgenic CD4(+) T cells and kill these autoreactive cells more efficiently than the immature CD11b(-) fraction. Together, these data suggest a protective role of mature NK cells in EAE, possibly through direct modulation of T cells inside the CNS, and demonstrate that mature and immature NK cells are recruited into the CNS by distinct chemotactic signals.

Exposure to Mild Hypoxia Associated with Oral Breathing Affects The NK Cell Ratio in The Spleen

Exposure to Mild Hypoxia Associated with Oral Breathing Affects The NK Cell Ratio in The Spleen

Immunophenotyping of cerebrospinal fluid cells in virus-associated neurologic diseases

OBJECTIVE: To characterize the cellular immunophenotype of cells in cerebrospinal fluid (CSF) of patients with virus-associated neurologic diseases. BACKGROUND: Various inflammatory neurologic diseases are associated with viral infections. These agents may cause direct damage of infected cells associated with immunological alterations such as chronic activation, immunodeficiency and infiltration of inflammatory cells into the CNS that underlie the pathogenesis of inflammatory neurologic diseases. Therefore, characterization of local immune responses that are associated with the inflammatory milieu may provide evidence or pathogenic “signature” of an immunopathogenic process in virus-associated neurologic diseases. DESIGN/METHODS: Multicolor flow cytometry is used to characterize CD4+ and CD8+ T cells, B cells, monocytes and NK cells in the CSF and blood of patients with virus-associated neurologic diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP; n=16), HIV adequately treated with antiretroviral drugs (n=16), multiple sclerosis (MS; n=4) and progressive multifocal leukoencephalopathy (PML; n=6) compared to healthy volunteers (n=6). RESULTS: In all patients, T cells were the predominant population in the CSF. CD4+ and CD8+ T cells were significantly altered among the groups, and the CD4/CD8 ratio reduced in HIV, HAM/TSP and a subset of PML, but elevated in MS. In patients with HAM/TSP, activated CD4+ T cells were significantly increased in the CSF as well as the blood and correlated with HTLV-1 proviral DNA loads. MS patients had a decreased frequency of effector/memory CD4+ and CD8+ T cells in the CSF. B cells and antibody producing plasma cells were elevated in patients with HAM/TSP, MS and PML whereas monocytes were reduced. CD56bright/CD56dim NK cell ratio was elevated in the CSF of patients with HAM/TSP. CONCLUSIONS: Immunophenotyping of CSF cells may reflect immune pathology in inflammatory neurologic diseases and can serve to highlight differential diagnoses that may lead to a better understanding of disease pathogenesis and clinical treatment. Disclosure: Dr. Akahata has nothing to disclose. Dr. Massoud has nothing to disclose. Dr. Caruso has nothing to disclose. Dr. Ohayon has nothing to disclose. Dr. Billioux has nothing to disclose. Dr. Von Geldern has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Nath has nothing to disclose. Dr. Jacobson has nothing to disclose.

Influence of autologous dendritic cells on the in-vitro expansion and functions of peripheral blood NK cells

Context: Allogeneic reactive NK cells were previously shown to exert a graft-versus-leukemia (GVL) effect during allogeneic hematopoietic stem cell transplantation, as well as reduce the incidence of graft-versus-host disease (GVHD).Objective: We used autologous immature DCs as feeder cells for the in-vitro expansion of NK cells and studied the function of the NK cell cultures.Materials and methods: NK cells were cultured for 15 days in the presence of autologous, immature DCs. Fold expansion, killing activity and expression of IFN-γ, perforin and granzyme B were evaluated.Results: The highest NK cell expansion efficiency was observed when the ratio of NK cells:DCs was 2:1 and when cells were cultured in a contact-dependent manner. The killing activity of NK cells was highest when the NK:DC ratio was 10:1. NK cell cultures exhibited a significant upregulation in the mRNA expression of IFN-γ, perforin and granzyme B when the ratio of NK cells to DCs was 10:1.Discussion: We successfully amplified NK cells using autologous immature DCs derived from human peripheral monocytes after induction as feeder cells. The use of autologous immature DCs for ex-vivo expansion of NK cells can be clinically applied to overcome limitations, such as the small number of NK cells in peripheral blood, and the high cost of NK cell sorting. Transfusion of allogeneic reactive NK cells has been suggested as a potential adjunctive therapeutic strategy after transplantation.Conclusion: Autologous immature DCs can be used as feeder cells for ex-vivo expansion of functional NK cells.

The effect of Kaqun-water on the immune parameters of healthy volunteers

Kaqun-water contains a high amount of stable oxygen, which absorbed through the skin and intestinal tract, increases tissue oxygenation. The aim of the authors was to evaluate the effect of 21 days of Kaqun-water treatment on the immune parameters of healthy volunteers. Subpopulations of lymphocytes were determined by immune phenotyping, and CD25 and CD71 activation antigens were used to assess lymphocyte activation. Production of reactive oxygen intermediates was measured to determine the killing capacity of neutrophil granulocytes. Data was analysed with repeated measures ANOVA. The reactive oxygen intermediate production of neutrophils increased significantly in stimulated samples during three weeks of Kaqun-water treatment. The percent of activated, CD25 positive T and helper T cells, and the ratio of NK cells increased. The increase in oxygen concentration caused by Kaqun-water treatment affects several immune functions: the killing potential of neurophil granulocytes is enhanced, the activation of lymphocytes shows an increased activity of immune function, and the elevated ratio of NK cells may help combat virally infected and tumorous cells.

HPV16 E2 protein promotes innate immunity by modulating immunosuppressive status

The balance between active immune responses against human papillomavirus (HPV) and HPV-induced immune escape regulates viral clearance and carcinogenesis. To understand the role of the early viral protein HPV16 E2 in host innate immune responses, the HPV16 E2-transfected murine squamous cell carcinoma cell line SCCVII (SCC/E2) was generated and anti-tumor responses in T-cell-depleted mice were evaluated. Tumor growth of SCC/E2 was markedly reduced. Cytotoxicity against the NK-sensitive targets YAC-1 and SCCVII was clearly enhanced in SCC/E2-inoculated mice. Despite the comparable ratio of NK cells, the proportion of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) was significantly decreased in SCC/E2-inoculated mice. The transcription of MDSC-related mediators such as inducible nitric oxide synthase, indoleamine 2,3-dioxygenase, and heme oxygenase-1 was significantly impaired in the SCC/E2-inoculated tumor tissues on day 3. Our results suggest that HPV16 E2 promotes anti-tumor innate effector function by modulating immunoregulatory events mediated by MDSCs and their mediators. This report describes a new role for HPV16 E2 as a local immunomodulator at infected sites.

Effects of laparoscopic radical surgery to gastric cancer on cellular immune functions

Objective To observe the effect of laparoscop radical surgery to gastric cancer on cellular immune functions.Methods 102 cases of advanced gastric cancer were divided into laparoscopy group (53 cases) and abdominal open surgery group (49 cases),given laparoscopic radical surgery and abdominal open surgery,respectively.The changes in CD3,CD4 +,CD8 +,CD19 and NK cells were examined by using flow cytometry on the preoperative day 1,and on the pest-operative day 1 and 5.Results The blood loss in laparoscopic (82.50 ± 50.33 ml) was significantly less than in abdominal open surgery group (107.50 ± 49.42 ml) (P ＜0.05).Propertion of CD3,CD4+,CD8+,CD19 and NK cells on the postoperative day 1 and 5 was significantly reduced in both groups as compared with that preoperation (P ＜0.05).There was significant difference in the NK cell ratio before and after operation between two groups (x2 =0.017,P ＜ 0.05).Conclusion Laparoscop radical surgery to gastric cancer was minimally invasive,and had slight effect on cellular immune functions. Key words: Gastric carcinoma; Laparoscope; Cell immunity

Natural killer and natural killer T-like cells in splenectomised patients

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Grywalska E, Markowicz J, Siwicka D, et al. Natural killer and natural killer T-like cells in splenectomised patients. Central European Journal of Immunology. 2013;38(3):372-379. doi:10.5114/ceji.2013.37759. APA Grywalska, E., Markowicz, J., Siwicka, D., Pasiarski, M., Surdacka, A., & Grafka, A. et al. (2013). Natural killer and natural killer T-like cells in splenectomised patients. Central European Journal of Immunology, 38(3), 372-379. https://doi.org/10.5114/ceji.2013.37759 Chicago Grywalska, Ewelina, Justyna Markowicz, Dorota Siwicka, Marcin Pasiarski, Agata Surdacka, Agnieszka Grafka, and Agnieszka Malec et al. 2013. "Natural killer and natural killer T-like cells in splenectomised patients". Central European Journal of Immunology 38 (3): 372-379. doi:10.5114/ceji.2013.37759. Harvard Grywalska, E., Markowicz, J., Siwicka, D., Pasiarski, M., Surdacka, A., Grafka, A., Malec, A., Bilski, M., Roman, T., and Roliński, J. (2013). Natural killer and natural killer T-like cells in splenectomised patients. Central European Journal of Immunology, 38(3), pp.372-379. https://doi.org/10.5114/ceji.2013.37759 MLA Grywalska, Ewelina et al. "Natural killer and natural killer T-like cells in splenectomised patients." Central European Journal of Immunology, vol. 38, no. 3, 2013, pp. 372-379. doi:10.5114/ceji.2013.37759. Vancouver Grywalska E, Markowicz J, Siwicka D, Pasiarski M, Surdacka A, Grafka A et al. Natural killer and natural killer T-like cells in splenectomised patients. Central European Journal of Immunology. 2013;38(3):372-379. doi:10.5114/ceji.2013.37759.

Nicotinamide (NAM) Increases Surface Expression of CD62L On in Vitro Expanded NK Cells

AbstractAbstract 4355Natural killer (NK) cells comprise a critical component of the innate immune system that controls infections and tumor transformation. Although proof of principle supporting the antitumor effects of adoptively infused autologous and allogeneic NK cells has been established, overall response rates appear low, possibly related to their inability to traffic to lymphoid tissues and the bone marrow where hematological malignancies such as AML, lymphomas, and multiple myeloma reside. CD62L receptors play a critical role in the recruitment of NK cells from the circulation to the bone marrow and lymph nodes. Recently, investigators have developed a number of approaches to expand NK cells ex vivo for adoptive infusion in patients with cancer. Although NK cells cultured with irradiated EBV transformed lymphoblastoid cell lines (EBV-LCL) can be expanded by more than 1000 fold and are more cytotoxic to tumor cells compared to resting or IL-2 activated NK cells, these expanded cells undergo a substantial reduction in CD62L surface expression which could hinder their ability to be recruited into the tumor microenvironment. NAM, a specific inhibitor of NAD (+) dependent enzymes, was shown to up-regulate surface expression of CD62L on freshly isolated NK cells cultured in feeder cell-free cytokine-containing media. Based on this observation, we hypothesized that CD62L expression would be increased on NK cells expanded ex vivo using EBV-LCL feeders by adding NAM to the culture media. Methods:Human NK cells were isolated from PBMCs of 5 healthy volunteers by depleting CD3+ T cells and subsequently selecting CD56+ cells using immuno-magnetic beads. NK cells were expanded ex vivo in flasks over 21 days by co-culturing with an irradiated EBV-LCL feeder cell line at 20:1 LCL to NK cell ratio in media containing 500 IU/mL of IL-2. NAM was added to the media on culture day 7 at a 5 mM or 7.5 mM concentration and expanded NK cells were evaluated every 2–3 days by FACS to assess their phenotype and viability and by cytotoxicity assays to assess their cytotoxicity against K562 and renal cell carcinoma targets. The effects of NAM on the proliferative capacity of ex vivo expanded NK cultures were likewise assessed. Results:NK cell expansion cultures containing NAM had substantially higher CD62L surface expression compared to cultures without NAM, with this effect being most pronounced in NK cell cultures containing the higher concentration (7.5 mM) of NAM (see figure). On NK cell culture days 12, 14, 16, and 21, the surface MFI of CD62L was a median 1.62, 2.44, 2.03 and 3.65 fold higher on NK cells cultured in 7.5 mM of NAM compared to cultures without NAM (p =0.017, 0.012, 0.037 and 0.046 respectively; paired t-test). No significant difference in surface expression of NK cell TRAIL, NKG2D, NKG2A, NKp30, NKp46, KIR2DL1, KIR3DL1, KIR2DL2/DL3, CD44, CD95, and CD200R was observed between NAM containing cultures and controls although NKp44 expression was slightly higher in cultures that did not contain NAM. NAM-treated and untreated NK cells had similar cytotoxic function against K562 and renal cell carcinoma (RCC) tumor cell lines. The viability of NK cells, assessed by Trypan Blue and Annexin V staining, was unaffected by NAM. The addition of NAM to cell culture media did result in a dose-dependent reduction in ex vivo NK cell expansion: on days 14 and 16, NK cells expanded a median 926 and 2963 fold in control media compared to a median 443 and 1151 fold in media containing 5 mM NAM (p=0.0029 and 0.0074 respectively) and a median 359 and 732 fold in media containing 7.5 mM NAM (p=0.0019 and 0.0003 respectively). Although the proliferation of NK cells was reduced, ex vivo expansion of NK cells still occurred in NAM containing media with NK cells expanding a median 2785 and 1360 fold by day 18 in cultures containing 5 and 7.5 mM of NAM, respectively. Conclusion:The addition of NAM to NK cell expansion cultures substantially increased surface expression of CD62L on NK cells without any deleterious effect on their cytotoxic function. Although NAM reduced ex vivo NK cell proliferation, NK cells still expanded more than 1000 fold in NAM containing media. These data suggest NAM-induced increases in CD62L surface expression could be used as a novel method to improve the homing capacity of ex vivo expanded NK cells to the bone marrow and the lymphoid organs, potentially enhancing their antitumor effects when adoptively infused in patients with hematological malignancies. [Display omitted] Disclosures:Peled:Gamida Cell Ltd. Cell Therapy Technologies: Employment. Frei:Gamida Cell Ltd. Cell Therapy Technologies: Employment.

Effects of a Home-based Exercise Program for Patients with Stomach Cancer Receiving Oral Chemotherapy after Surgery

The purpose of this study was to identify the effects of a home based exercise program for patients with stomach cancer who were undergoing oral chemotherapy. The home-based exercise program was developed from the study findings of Winningham (1990) and data from the Korea Athletic Promotion Association (2007). The home-based exercise program consisted of 8 weeks of individual exercise education and exercise adherence strategy. Participants were 24 patients with stomach cancer who were undergoing oral chemotherapy following surgery in 2007 or 2008 at a university hospital in Seoul. Patients were randomly assigned to either the experimental group (11) or control group (13). The effects of the home-based exercise program were measured by level of cancer related fatigue, NK cell ratio, anxiety, and quality of life. Data were analyzed using SPSS/WIN 13.0 version. The degree of cancer related fatigue and anxiety in the experimental group decreased compared to the control group. The NK cell ratio and the degree of quality of life of experimental group increased while that of the control group decreased. This study result indicate the importance of exercise and provide empirical evidence for continuation of safe exercise for patients with cancer during their chemotherapy.

Minimal Residual Disease (MRD) and T/NK Cell Dynamics during Fludarabine, Cyclophosphamide Plus Rituximab (FCR) Followed by Fludarabine Plus Rituximab (FR) and Remission Maintenance Therapy with Rituximab in Previously Untreated B-Chronic Lymphocytic Leukemia (B-CLL): Riskfactor Stratification in the Chairos Study

Based on the efficacy of Fludarabine, Cyclophosphamide plus Rituximab (FCR) as first-line therapy for chronic lymphocytic leukemia (CLL), we conducted a non-randomized multi-center phase II trial with early brief intensive induction with FCR for 3 cycles followed by fludarabine/rituximab for 3 cycles. In addition patients received a 2 year 3-monthly rituximab maintenance regimen. The trial recruited 42 patients. Clinical baseline data, clinical response results and toxicity of a planned first interim analysis were reported previously (Egle et al, ASH 2007). We now present the data from flow cytometric minimal residual disease (MRD) monitoring during the study in combination with the performed risk factor analyses and report on the findings of detailed analysis of T-cell and NK cell dynamics during the induction phase of the trial. From the previously reported high number of CRs (94% after complete 6 cycle induction) 64% were MRD negative by flow cytometric definition (less than 10−3 G/L CLL cells). All non CR patients were correctly called as MRD positive. Less than 0.1 G/L CLL cells after 3 cycles of FCR identified all patients achieving MDR negativity after the complete induction regimen. CD30 risk, as well as age, FISH cytogenetic analysis and analysis of IgVH mutation status were analysed for their impact on MRD dynamics. We could not find any difference in MRD responses between CD38 high and low risk groups or between age groups (> and <65a). Neither did abberations found in FISH cytogenetics predict the MRD responses and all CLL patients harboring an 11q deletion achieved MRD negativity. Interestingly, we found the only predictive factor to be the IgVH mutation status with 15 unmutated CLL patients significantly less likely to achieve MRD negativity after induction treatment (p=0,025). Especially, three patients with rearranged IgVH 3–21 did poorly, suggesting that these patients may need a different therapeutic approach. Six months of Rituximab maintenance therapy were able to convert 37% of patients from MRD positive state after remission induction to a MRD negative state. T and NK cell numbers and ratios were followed during therapy. In addition T cell subsets and their CD38 expression status were analysed. While absolute T and NK/NKT cell numbers decreased dramatically during treatment (CD4 and CD8 cell numbers decreased to medians of less than 100/μl after 6 cycles of induction treatment), a count of less than 200 CD4 cells/μl after 3 cycles of FCR was found to be predictive of MRD negativity. In addition, we observed an earlier recovery of NK and NKT cells after the end of induction treatment leading to an inverted NK(T) to T cell ratio early during maintenance treatment. This may have implications for NK-dependent ADCC during rituximab maintenance therapy. Regarding the CD4 and CD8 compartment we observed in addition to the reduction in absolute numbers a marked shift of T cell subsets. Naïve T cells were more completely depleted by FCR/FR treatment than T cells from the memory compartment, with central memory (CM) CD4 cells increasing from a median of 49% to 79%. This was less pronounced in the CD8 compartment. CD38 expression on T cells was monitored, because our group found that this was predictive of CLL course (Tinhofer Blood 2006). Interestingly we found a marked increase of the proportional representation of CD38+ CD8 and CD4 T cells in the T cell compartment with a more pronounced effect observed in the CD8 compartment. CD8 T cell counts were also quicker to recover during rituximab maintenance therapy. While these data point to essential caveats regarding the immunosuppressive toxicity of the treatment, they may also point to a window of opportunity regarding the modification of T cell responses during the phase of immune reconstitution after FCR/FR therapy. In conclusion we find that only IgVH mutation status was predictive of achievement of MRD negativity and we could show significant skewing of T cell and NK(T) cell subsets during chemoimmunotherapy. A better understanding of these T/NK cell dynamics may lead to the development of improved targeting of the immune recovery phase after chemotherapy using immunomodulating maintenance strategies.

Commentary 2

Although recognized more than 150 years ago, hidradenitis suppurativa (HS) is still a mysterious disease. Ever since inflammation of the apocrine glands was recognized as a secondary event in the pathogenesis of the disease, it has been speculated that comedonal and/or poral occlusion(s) and bacterial infection play a crucial role. Even though this concept has been questioned almost immediately, there is some consensus regarding the role of immunity and infection. Thus, even if I cannot provide an answer to the question posed by the editor, let me elaborate on the issues of skin immune response and infection in HS pathogenesis. The involvement of immune response in HS remains controversial. Immunological investigations of patients with HS suggested no abnormalities of the immune system (1). By contrast, other authors showed increased peripheral suppressor T-cell activity (2), indicative of a cellular immune response. This is further supported by the presence of activated, HLA-DR-positive as well as Leu-8-positive immunoregulatory lymphocytes (3). These results indicate that the lymphocytic infiltrate is definitely the result of in vivo activation of lymphoid cells. Indeed, the significant fall of the T-helper/suppressor and NK cell ratio over time after the initiation supports the existence of a precipitating, cell-mediated immune response with only a short eliciting period (3,4). More recent studies have shown that dysfunctional neutrophils and monocytes may also be involved in the pathogenesis of HS, still, no primary abnormalities of the innate or acquired immune system can be held to be causal in every case (3–6). Because of increasing evidence suggesting that keratinocytes (KCs) not only participate in cutaneous immune responses but may in fact play key initiation roles (7), one must also consider the contribution of KCs to HS pathogenesis. KCs are able to recognize a wide variety of micro-organisms through their pattern recognition receptors (PRRs) and have evolved mechanisms to distinguish between skin commensals and pathogens. Signalling through specific PRR combinations provides selectivity and specificity to immune response. As a result, KCs produce a wide range of antimicrobial peptides, proinflammatory cytokines/chemokines and inducible enzymes (8). The secretion of antimicrobial peptides is indeed crucial, as skin lesions characterized by low levels of such host-defence peptides are more susceptible to infections. By exhibiting chemoattractant activity, KC-derived cytokines/chemokines and antimicrobial peptides can recruit T cells, neutrophils and dendritic cells into sites of infection, thus providing an improved immune response against pathogens (7,8). These findings indicate a close interdependence of KCs and inflammatory infiltrate as well as a balance between the innate and acquired immune systems. Any perturbation in this system, for example dysregulation and abnormal expression of inflammatory mediators or their receptors in KCs, can lead to the pathogenesis of chronic inflammatory skin diseases, such as HS. The significance of bacterial involvement in the pathogenesis of HS is also controversial. It is likely that chronic inflammation is because of secondary bacterial colonization (5). This is further supported by the fact that routine cultures from the surface of the lesions are often negative. Still, bacteria are likely to be involved in the pathogenesis of the disease as numerous species are most frequently isolated from lesions (6,9). Most of bacteria identified in HS lesions, such as Propionibacterium acnes and coagulase-negative staphylococci, are part of the normal microflora, but have also gained attention as pathogens. These findings highlight a possible polymicrobial nature and predominance of anaerobic bacteria, supporting the role of bacterial infections as a possible pathogenic event in HS. However, interpreting the results of previous studies is difficult, as potential differences amongst recently discovered phylogenetic groups and/or ecotypes have not been taken into account. Notably, the existence of philogenetically distinct P. acnes clusters have recently been demonstrated (10). Importantly, these clusters differ in the production of secreted proteins (11), and induce different immune responses in KCs and sebocytes (12,13). These findings challenge our current understanding of the pathogenic nature of bacteria involved in HS pathogenesis and raise the exciting possibility that bacterial strains, or group of strains, with greater potential to cause opportunistic infection in HS may exist. This may explain, in part, the apparent controversy with respect to the role of bacterial infection in HS.

Clinical research of the malignant hydrothorax or hydroperitoneum treated with intracavitary chemotherapy and local thermotherapy

19615 Background: Malignant hydrothorax or hydroperitoneum are common complications of the cancer. Pure chemotherapy couldn’t get good effect. We combined intracavitary chemotherapy with local thermotherapy to cure malignant hydrothorax or hydroperitoneum. In order to observe the recent effects and toxicity of thermochemotherapy and evaluate the change of the immunologic function, and to investigate the mechanism of thermochemotherapy. Methods: Fifty-two patients were treated with weekly intracavitary chemotherapy, and then combined with local thermotherapy twice a week. As the control, another fifty patients received weekly intracavitary chemotherapy. Treated for two weeks and rest for one week, and then observed the recent effects and toxicity. Test the level of the T cell subset, NK cells and VEGF in serum and effusion Results: Overall response rate of the malignant hydrothorax was 86.9% vs 60.0% (P&lt;0.05), Overall response rate of the malignant hydroperitoneum was 79.3% vs 46.7% (P &lt;0.01).The incidence of myelosuppression was 7.7% vs 24% (P&lt;0.05). After thermochemotherapy, the ratio of CD4/CD8 rose significantly (P&lt;0.01), but the ratio of NK cells decreased significantly (P&lt;0.05) in malignant hydrothorax or hydroperitoneum. While in peripheral blood, all the ratio of CD3, CD4, CD8, CD4/CD8 and NK cells rose significantly (P&lt;0.05). Meanwhile the level of VEGF decreased significantly (P&lt;0.05) whether in effusion or blood. Conclusions: Combined intracavitary chemotherapy with local thermotherapy could control the malignant hydrothorax and hydroperitoneum effectively with less-toxicity. The cellular immune function was elevated and the neovascularization of tumor was probablely inhibited. No significant financial relationships to disclose.