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1.
Bert De Klerck Isabelle Carpentier Rik J Lories Yvette Habraken Jacques Piette Geert Carmeliet Rudi Beyaert Alfons Billiau Patrick Matthys 《Arthritis research & therapy》2004,6(3):R220
Collagen-induced arthritis (CIA) in mice is accompanied by splenomegaly due to the selective expansion of immature CD11b+ myeloblasts. Both disease manifestations are more pronounced in interferon-γ receptor knock-out (IFN-γR KO) mice. We have
taken advantage of this difference to test the hypothesis that the expanding CD11b+ splenic cell population constitutes a source from which osteoclast precursors are recruited to the joint synovia. We found
larger numbers of osteoclasts and more severe bone destruction in joints of IFN-γR KO mice than in joints of wild-type mice.
Osteoclast-like multinucleated cells appeared in splenocyte cultures established in the presence of macrophage colony-stimulating
factor (M-CSF) and stimulated with the osteoclast-differentiating factor receptor activator of NF-κB ligand (RANKL) or with
tumour necrosis factor-α (TNF-α). Significantly larger numbers of such cells could be generated from splenocytes of IFN-γR
KO mice than from those of wild-type mice. This was not accompanied, as might have been expected, by increased concentrations
of the intracellular adaptor protein TRAF6, known to be involved in signalling of RANKL- and TNF-α-induced osteoclast formation.
Splenocyte cultures of IFN-γR KO mice also produced more TNF-α and more RANKL than those of wild-type mice. Finally, splenocytes
isolated from immunised IFN-γR KO mice contained comparatively low levels of pro-interleukin-1β (pro-IL-1β) and pro-caspase-1,
indicating more extensive conversion of pro-IL-1β into secreted active IL-1β. These observations provide evidence that all
conditions are fulfilled for the expanding CD11b+ splenocytes to act as a source of osteoclasts and to be indirectly responsible for bone destruction in CIA. They also provide
a plausible explanation for the higher susceptibility of IFN-γR KO mice to CIA. 相似文献
2.
Ahn G Hwang I Park E Kim J Jeon YJ Lee J Park JW Jee Y 《Marine biotechnology (New York, N.Y.)》2008,10(3):278-289
We investigated whether the brown seaweed Alariaceae Ecklonia cava (E. cava) has immunological effects on splenocytes in vitro. For that purpose, we prepared an enzymatic extract from E. cava (ECK) by using the protease, Kojizyme. Here, ECK administered to ICR mice dramatically enhanced the proliferation of their
splenocytes and increased the number of their lymphocytes, monocytes and granulocytes. In flow cytometry assays performed
to identify in detail the specific phenotypes of these proliferating cells after ECK treatment, the numbers of CD4+ T cells, CD8+ T cells and CD45R/B220+ B cells increased significantly compared to those in untreated controls. In addition, the mRNA expression and production
level of Th1-type cytokines, i.e., TNF-α and IFN-γ, were down-regulated, whereas those of Th2-type cytokines, i.e., IL-4 and
IL-10, were up-regulated by ECK. Overall, this dramatic increase in numbers of splenocytes indicated that ECK could induce
these cells to proliferate and could regulate the production of Th1- as well as Th2-type cytokines in immune cells. These
results suggest that ECK has the immunomodulatory ability to activate the anti-inflammatory response and/or suppress the proinflammatory
response, thereby endorsing its usefulness as therapy for diseases of the immune system.
Y-J. Jeon and Y. Jee contributed equally to this study. 相似文献
3.
Ursula Elsässer-Beile Ulrich Wetterauer Wolfgang Schultze-Seemann Harald Gallati Jürgen Schulte Mönting Sabine von Kleist 《Cancer immunology, immunotherapy : CII》1996,42(2):93-98
The immunological properties of tumor-infiltrating (TIL) and peripheral blood lymphocytes (PBL) from 29 patients with renal
cell carcinomas were characterized with respect to their phenotypic expression and cytokine production. TIL were isolated
from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation. To eliminate all
non-lymphoid cells, CD3-positive cells were specifically separated from these cell fractions with anti-CD3 magnetic beads.
These pure CD3-positive PBL (CD3+PBL) and TIL (CD3+TIL) were cultured with pokeweed mitogen and the levels of the cytokines interleukin-1α (IL-1α), IL-1β, IL-2, interferon γ
(IFNγ), and tumor necrosis factor α (TNFα) measured in the 4-day post-inductional cell culture supernatants. In all cell cultures
a wide range of cytokine values was found, indicating a large variation in the immunological activity of the lymphocytes of
each individual. When the cell cultures of the CD3+TIL and CD3+PBL were compared in each patient similar values for IL-1α, IL-1β, IFNγ and TNFα were found. However CD3+TIL produced significantly lower levels of IL-2 than CD3+PBL upon mitogenic stimulation. This may be due to a lower CD4/CD8 ratio in the CD3+TIL as compared to the CD3+PBL. These results suggest that there are no fundamental qualitative and quantitative differences in the lymphokine-producing
capacity of CD3+TIL and CD3+PBL derived from patients with renal cell carcinomas.
Received: 8 August 1995 / Accepted: 23 January 1996 相似文献
4.
Nishijima K Hisatsune T Kato H Kohyama M Kakehi M Hachimura S Kaminogawa S 《Cytotechnology》1997,25(1-3):89-100
Feeding of a whole casein diet, which abolished the αs1-casein-specific proliferation and IFN-γ productivity of CD4+ T cells, did not affect the proliferative response of CD8+ T cells with regard to the antigen dose response, cell dose response, kinetics of the proliferation and epitope specificity,
as well as IFN-γ production. To assess the characteristics of the CD8+ T cells, we established αs1-casein-specific CD8+ T cell clones from both casein-fed and control mice. The established clones produced different amount of IFN-γ and IL-10,
and one clone derived from the casein-fed mice produced a remarkable amount of IL-10. The clones from casein-fed mice produced
considerable amounts of TGF-β, while those from control mice produced only small amounts. The possible role of CD8+ T cells in oral tolerance is discussed.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
5.
Production of interferons and change of the lymphocyte subpopulation phenotype in peripheral blood at cervical papillomavirus infection 总被引:3,自引:0,他引:3
Lazarenko L Spivak M Lakatosh V Kryvokhatska L Mikhailenko O Rudenko A Tkáciková L Mikula I 《Folia microbiologica》2002,47(6):747-752
IFN-γ and IFN-α productionin vitro by peripheral blood cells activated by phytohemagglutinin or the Newcastle disease virus was impaired in patients with a
benign process, cervical intraepithelial neoplasm and cancerin situ associated with human papillomavirus infection. In case of IFN-γ and IFN-α production impairment following cervical papillomavirus
infection, the increased severity of disease was accompanied by remarkable IFN system suppression. The lower synthesis of
both IFN correlated with changes of some lymphocyte-subpopulation phenotype in peripheral blood. Lower CD4+ and CD3+ DR+ T cell concentrations were observed in papillomavirus-infected patients with impaired IFN production; impaired IFN-γ production
was accompanied by lower CD4/CD8 index. 相似文献
6.
Developing a cancer vaccine with a potent adjuvant, which is safe for human use, remains to be an unmet need. In this study,
we developed a simple, safe, yet efficient, peptide-based therapeutic cancer vaccine, DOTAP/E7 complex, which comprises only
two molecules: a DOTAP cationic lipid and a peptide antigen derived from E7 oncoprotein of human papillomavirus (HPV) type
16. The anti-cancer activity of DOTAP/E7 against existing HPV positive TC-1 tumor was compared to that of our previous LPD/E7
formulation, which contains bacterial DNA CpG motifs. Tumor-bearing mice showed significant tumor inhibition following a single
vaccination of either formulation at the optimal lipid dose, suggesting that DOTAP liposome alone can provide a potent adjuvant
activity without plasmid DNA. E7 peptide formulated with DOTAP induced migration of activated dendritic cells (DC) to the
draining lymph node (DLN) and efficiently generated functional antigen-specific CD8+ T lymphocyte responses. Accumulation of CD8+ tumor infiltrating T cells and apoptosis at tumor sites were observed after treatment with DOTAP/E7 complexes, which was
also associated with a decreased amount of CD25+Foxp3+ regulatory T cells in treated animals. Reactive oxygen species (ROS) induced by DOTAP cationic lipid in DLN revealed a plausible
mechanism of the initial interaction between DC and DOTAP. An adequate amount of ROS generation was apparently required for
the initiation of the vaccine mechanism; however, an overdose of DOTAP induced massive ROS production and apoptosis of DC
in DLN, which led to diminished anti-cancer immunity. Overall, these results indicate that cationic lipid DOTAP alone serves
as an efficient vaccine adjuvant for the induction of a therapeutic, antigen-specific anti-cancer activity. 相似文献
7.
Yusuke Nakanishi Akira Hosono Yasuhiro Hiramatsu Teiji Kimura Ryo Nakamura Shuichi Kaminogawa 《Cytotechnology》2005,47(1-3):69-77
We demonstrate immunomodulatory effects, especially those involving murine intestinal IgA secretion, in Peyer's patch cells
following oral administration of Bifidobacterium immunomodulator (BIM) derived from sonicated B. pseudocatenulatum 7041. BALB/c mice were administered BIM orally for 7 consecutive days. The PP cells demonstrated upregulated secretion of
total IgA including BIM-specific IgA following BIM administration. In observing the response of PP cells co-cultured with
BIM, we found enhanced secretion of interferon-γ (IFN-γ) and interleukin (IL)-6 in the CD4+ T cells. In contrast, IL-12 secretion by Thy1.2− PP cells was enhanced, but secretion of IFN-γ, IL-5, and IL-6 was not significantly affected. Furthermore, the population
of CD4+ CD45RBhigh T cells in PP increased following oral administration of BIM. These data suggest that CD4+ T cells were affected by BIM administration. Overall, the results show that oral administration of BIM induced CD4+ PP cells to change their expression of cell surface antigen and cytokine production. 相似文献
8.
Guenterberg KD Lesinski GB Mundy-Bosse BL Karpa VI Jaime-Ramirez AC Wei L Carson WE 《Cancer immunology, immunotherapy : CII》2011,60(9):1281-1288
Interferon-alpha (IFN-α) is an immunomodulatory cytokine that is used clinically for the treatment of melanoma in the adjuvant
setting. The cellular actions of IFN-α are regulated by the suppressors of cytokine signaling (SOCS) family of proteins. We
hypothesized that the anti-tumor activity of exogenous IFN-α would be enhanced in SOCS1-deficient mice. SOCS1-deficient (SOCS1−/−) or control (SOCS1+/+) mice on an IFN-γ−/− C57BL/6 background bearing intraperitoneal (i.p.) JB/MS murine melanoma cells were treated for 30 days with i.p. injections
of IFN-A/D or PBS (vehicle). Log-rank Kaplan-Meier survival curves were used to evaluate survival. Tumor-bearing control SOCS1+/+ mice receiving IFN-A/D had significantly enhanced survival versus PBS–treated mice (P = 0.0048). The anti-tumor effects of IFN-A/D therapy were significantly enhanced in tumor-bearing SOCS1−/− mice; 75% of these mice survived tumor challenge, whereas PBS-treated SOCS1−/− mice all died at 13-16 days (P = 0.00038). Antibody (Ab) depletion of CD8+ T cells abrogated the anti-tumor effects of IFN-A/D in SOCS1−/− mice as compared with mice receiving a control antibody (P = 0.0021). CD4+ T-cell depletion from SOCS1−/− mice also inhibited the effects of IFN-A/D (P = 0.0003). IFN-A/D did not alter expression of CD80 or CD86 on splenocytes of SOCS1+/+ or SOCS1−/− mice, or the proportion of T regulatory cells or myeloid-derived suppressor cells in SOCS1+/+ or SOCS1−/− mice. An analysis of T-cell function did reveal increased proliferation of SOCS1-deficient splenocytes at baseline and in
response to mitogenic stimuli. These data suggest that modulation of SOCS1 function in T-cell subsets could enhance the anti-tumor
effects of IFN-α in the setting of melanoma. 相似文献
9.
Wu L Zhao L Zheng Q Shang F Wang X Wang L Lang B 《Molecular and cellular biochemistry》2006,284(1-2):65-71
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes guanosine or adenosine mononucleotide-dependent reversible conversion of oxaloacetate (OAA) and phosphoenolpyruvate (PEP). Mycobacterium (M) tuberculosis possesses a putative GTP-dependent PEPCK. To analyze the immune responses caused by PEPCK, the effects of PEPCK on the induction of CD4+ T cells and cytokines such as IFN-γ, IL-12 and TNF-α were evaluated in mice. It was found that the number of CD4+ T cells was increased in the PEPCK immunized mice although the change of the number of CD8+ T cells was not significant. The cytokines IFN-γ, IL-12 and TNF-α were increased significantly in the mice immunized with PEPCK than those of incomplete adjuvant. These characteristics were further demonstrated in the mice infected by pckA mutated BCG strain. The results indicate that PEPCK can effectively induce cell-mediated immune response by increasing activity of cytokines and PEPCK may be a promising new subunit vaccine candidate for tuberculosis. 相似文献
10.
Ursula Elsässer-Beile Thomas Grussenmeyer Dorothee Gierschner Barbara Schmoll Wolfgang Schultze-Seemann Ulrich Wetterauer Jürgen Schulte Mönting 《Cancer immunology, immunotherapy : CII》1999,48(4):204-208
The mRNA expression of Th1 and Th2 cytokines was compared in freshly isolated CD3+ tumor-infiltrating lymphocytes (CD3+ TIL) and in autologous CD3+ peripheral blood lymphocytes (CD3+ PBL) obtained simultaneously from 20 patients with renal cell carcinomas (RCC). In addition cytokine expression was compared
in CD4+ TIL and CD8+ TIL from another group of 20 patients with RCC. TIL were isolated from mechanically disaggregated tumor material and PBL
from peripheral blood by gradient centrifugation and subsequent selection with anti-CD3, anti-CD4 or anti-CD8 magnetic beads.
In these pure lymphocyte preparations the constitutive expression of interleukin-1 (IL-1), IL-2, IL-10, interferon γ (IFN),
and tumor necrosis factor α (TNF) was determined by using a polymerase-chain-reaction-assisted mRNA amplification assay. In
the CD3+ TIL, levels of mRNA for IFN, IL-10, IL-1 and TNF were significantly higher than in the autologous CD3+ PBL whereas IL-2 expression was rather low and did not differ in the two populations. Comparison of cytokine mRNA expression
in CD4+ TIL and simultaneously obtained CD8+ TIL revealed a significantly higher expression of IFN in the CD8+ cells. These data reflect an in vivo activation of RCC-infiltrating lymphocytes at the mRNA level with respect to the Th1
as well as the Th2 immune response. Th1 activation seems to be most evident in the CD8+ TIL.
Received: 14 January 1999 / Accepted: 30 April 1999 相似文献
11.
We have addressed the hypothesis that pathogen-associated immunomodulatory molecules may influence anti-tumor immunity through
their pro- and anti-inflammatory activities and abilities to induce effector and regulatory T (Treg) cells. We found that
CpG oligonucleotides (CpG) and cholera toxin (CT), which promote Th1 or Th2/Treg cell biased responses, respectively, had
differential effects on tumor growth. Therapeutic peritumoral administration of CpG significantly reduced subcutaneous tumor
growth and prolonged survival, whereas CT enhanced tumor growth and reduced survival. Peritumoral administration of CpG enhanced
the frequency of IFN-γ-secreting and reduced IL-10-secreting CD4+ and CD8+ T cells, in the tumor and in the draining lymph nodes, whereas, CT significantly enhanced the frequency of CD4+CD25+Foxp3+ Treg cells, but reduced IFN-γ-secreting T cells infiltrating the tumor. In contrast to the beneficial effect of CpG in mice
with subcutaneous tumors, CpG or CT had no protective effect against tumor growth in the lungs when given therapeutically
by the nasal route. However, prophylactic intranasal administration of CpG significantly reduced the number of lung metastases
and this was associated with an enhanced frequency of IFN-γ-secreting CD8+ T cells in the draining lymph node and enhanced tumor-specific CTL responses. Our findings demonstrate that pathogen-associated
molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory
T cells, and that the environment of the growing tumor influences the protective effect.
Joanne Lysaght and Andrew G. Jarnicki contributed equally. 相似文献
12.
De Klerck B Geboes L Hatse S Kelchtermans H Meyvis Y Vermeire K Bridger G Billiau A Schols D Matthys P 《Arthritis research & therapy》2005,7(6):R1208-R1220
CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the chemokine receptor CXCR4. We previously reported
that treatment with a specific CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of collagen-induced
arthritis (CIA) in the highly susceptible IFN-γ receptor-deficient (IFN-γR KO) mouse. We concluded that CXCL12 plays a central
role in the pathogenesis of CIA in IFN-γR KO mice by promoting delayed type hypersensitivity against the auto-antigen and
by interfering with chemotaxis of CXCR4+ cells to the inflamed joints. Here, we investigated whether AMD3100 can likewise inhibit CIA in wild-type mice and analysed
the underlying mechanism. Parenteral treatment with the drug at the time of onset of arthritis reduced disease incidence and
modestly inhibited severity in affected mice. This beneficial effect was associated with reduced serum concentrations of IL-6.
AMD3100 did not affect anti-collagen type II antibodies and, in contrast with its action in IFN-γR KO mice, did not inhibit
the delayed type hypersensitivity response against collagen type II, suggesting that the beneficial effect cannot be explained
by inhibition of humoral or cellular autoimmune responses. AMD3100 inhibited the in vitro chemotactic effect of CXCL12 on splenocytes, as well as in vivo leukocyte infiltration in CXCL12-containing subcutaneous air pouches. We also demonstrate that, in addition to its effect
on cell infiltration, CXCL12 potentiates receptor activator of NF-κB ligand-induced osteoclast differentiation from splenocytes
and increases the calcium phosphate-resorbing capacity of these osteoclasts, both processes being potently counteracted by
AMD3100. Our observations indicate that CXCL12 acts as a pro-inflammatory factor in the pathogenesis of autoimmune arthritis
by attracting inflammatory cells to joints and by stimulating the differentiation and activation of osteoclasts. 相似文献
13.
Cytotoxic T cells infiltrating a glioma express an aberrant phenotype that is associated with decreased function and apoptosis 总被引:5,自引:0,他引:5
In this study, we report on novel alterations found in rat intracranial (i.c.) tumor-infiltrating T lymphocytes (TIL) that
are indicative of T cell defects and death. FACS analysis showed that the cytotoxic T cells (CTL) infiltrating rat T9.F gliomas
were CD3ɛ+, αβTCR+, CD8α
+, but CD8β
−. These lymphocytes also stained positive for the B cell-specific marker, CD45RA, as well as Annexin-V, signifying apoptotic
changes. Functional and biochemical analyses were performed to assess whether the aberrant phenotype was linked to other defects.
When CD8α
+ TIL were purified and stimulated in vitro, their proliferative capacity was markedly diminished in comparison with CD3+CD8α
+CD8β
+ T cells isolated from the spleens of naive, non tumor-bearing rats. Furthermore, the mean fluorescence intensity of surface
CD3ɛ was dramatically reduced in the CD3+CD8α
+CD8β
− TIL population as compared with CD3+CD8α
+CD8β
+ TIL from the same tumor-bearing animal. Biochemical studies revealed that the expression of TCRζ and LAT were reduced in
lysates generated from CD8α-purified TIL with respect to CD8α-purified T cells from naive spleen. We believe that these degenerative changes are reflective of chronic T cell receptor
ligation, because in vitro culture of rat splenocytes or purified T cells with ConA or anti-CD3 mAb induced the same alterations.
In vitro, the downregulation of CD8β could be inhibited by the caspase inhibitor, z-VAD. These results suggest that the aberrant CTL phenotype found in the TIL
of glioma-bearing rats may be novel signals for their impending death and degenerating anti-tumor immune function.
Received: 27 February 2001 / Accepted: 26 April 2001 相似文献
14.
Marie A. Salmeron Tatsuo Morita Hidetoshi Seki Chris D. Platsoucas Kyogo Itoh 《Cancer immunology, immunotherapy : CII》1992,35(3):211-217
Summary Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was studied. Uncultured TIL produced interferon (IFN), but not interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity (CTL-TIL) produced IFN in culture with medium alone, whereas IL-2-activated noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up-regulated IFN production in IL-2-activated TIL from 10 of 12 or 6 of 12 cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL) produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4+ and 1 CD8+) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4+ and 1 CD8+) of 7 noncytotoxic TIL clones produced IFN in culture with medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN-producing CTL clones tested produced IL-2 in 4 ×-concentrated supernatants from a 3.5-h culture with medium alone. Furthermore, 2 IFN-producing CTL clones tested expressed mRNA for both IFN and IL-2. IL-2 production and its mRNA expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or autologous tumor cells. IL-4 production was not observed in culture either with medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones, and none of 5 noncytotoxic TIL clones. In summary, IFN production was characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are suggested to be productive of IL-2 and IFN under unstimulated conditions, both being required for self-activation in an autocrine loop.This work was supported in part by grant CA-47891 from the National Cancer Institute 相似文献
15.
IL-10, IL-13, IFN-γ, tumor necrosis factor (TNF)-α, LT-α, CD154, and TNF-related activation-induced cytokine (TRANCE) were expressed by 2-20% of rheumatoid arthritis (RA) synovial tissue CD4+ memory T cells, whereas CD4+ cells that produced IL-2, IL-4, or IL-6 were not detected. Expression of none of these molecules by individual CD4+ cells correlated with the exception of TRANCE and IL-10, and TRANCE and TNF-α. A correlation between expression of IL-10 and CCR7, LT-α and CCR6, IFN-γ and CCR5, and TRANCE and CXCR4 was also detected. 相似文献
16.
Promoting effect of Antrodia camphorata as an immunomodulating adjuvant on the antitumor efficacy of HER-2/neu DNA vaccine 总被引:1,自引:0,他引:1
Chia-Hsin Huang Chia-Che Chang Chiu-Mei Lin Sin-Ting Wang Min-Tze Wu Eric I. C. Li Hsien-Chang Chang Chi-Chen Lin 《Cancer immunology, immunotherapy : CII》2010,59(8):1259-1272
It is well known that DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models.
Antrodia camphorata (AC) is a unique basidiomycete fungus of the Polyporaceae family that only grows on the aromatic tree Cinnamomum kanehirai Hayata (Lauraceae) endemic to Taiwan. Importantly, AC has been shown to be highly beneficial in the treatment and prevention of cancer. The
goal of this study was to investigate whether AC is able to augment the antitumor immune properties of a HER-2/neu DNA vaccine
in a mouse model in which p185neu is overexpressed in MBT-2 tumor cells. Compared with the mice that received the HER-2/neu
DNA vaccine alone, co-treatment with AC suppressed tumor growth and extended the survival rate. This increase in the antitumor
efficacy was attributed to the enhancement of the Th1-like cellular immune response by the HER-2/neu DNA vaccine–AC combination.
Evidence for this came from the marked increase in the IFN-γ mRNA expression in CD4+ T cells in the draining inguinal lymph nodes, an increase in the number of functional HER-2/neu-specific CTLs, and the increased
tumor infiltration of both CD4+ and CD8+ T cells, depletion of which abolishes the antitumor effect of the HER-2/neu DNA vaccine–AC therapy. Our results further indicate
that the treatment of mice with AC enhanced DC activation and production of Th1-activating cytokines (e.g. IL-12, and IFN-α)
in the draining lymph nodes, which were sufficient to directly stimulate T cell proliferation and higher IFN-γ production
in response to ErbB2. Overall, these results clearly demonstrate that AC represents a promising immunomodulatory adjuvant
that could enhance the therapeutic potency of HER-2/neu DNA vaccines in cancer therapy. 相似文献
17.
Gao Y Zhang D Sun B Fujii H Kosuna K Yin Z 《Cancer immunology, immunotherapy : CII》2006,55(10):1258-1266
Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4+ and CD8+ T cells, increased the number of tumor Ag-specific CD8+ T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-γ producing CD8+ T cells. Interestingly, AHCC treatment also showed increased cell number of NK and γδ T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses. 相似文献
18.
Tumor‐Targeting Salmonella typhimurium A1‐R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic‐Cancer Orthotopic Mouse Model 下载免费PDF全文
Takashi Murakami Yukihiko Hiroshima Yong Zhang Ming Zhao Tasuku Kiyuna Ho Kyoung Hwang Kentaro Miyake Yuki Homma Ryutaro Mori Ryusei Matsuyama Takashi Chishima Yasushi Ichikawa Kuniya Tanaka Michael Bouvet Itaru Endo Robert M. Hoffman 《Journal of cellular biochemistry》2018,119(1):634-639
The present study determined the effect of the tumor‐targeting strain Salmonella typhimurium A1‐R (S. typhimurium A1‐R) on CD8+ tumor‐infiltrating lymphocytes (TILs) in a syngeneic pancreatic‐cancer orthotopic mouse model. The effect of tumor‐targeting S. typhimurium A1‐R on CD8+ TILs was determined on the Pan02 murine pancreatic‐adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1‐R‐treatment group (n = 8, 1 × 107 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor‐volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1‐R‐treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1‐R‐treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti‐mouse CD8+ antibody was performed in order to detect TILs determined by calculating the average number of CD8+ cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1‐R promotes CD8+ T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634–639, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
19.
We previously found that chronic alcohol consumption decreases the survival of mice bearing subcutaneous B16BL6 melanoma.
The underlying mechanism is still not completely understood. Antitumor T cell immune responses are important to inhibiting
tumor progression and extending survival. Therefore, we examined the effects of chronic alcohol consumption on the functionality
and regulation of these cells in C57BL/6 mice that chronically consumed 20% (w/v) alcohol and subsequently were inoculated
subcutaneously with B16BL6 melanoma cells. Chronic alcohol consumption inhibited melanoma-induced memory T cell expansion
and accelerated the decay of interferon (IFN)-γ producing T cells in the tumor-bearing mice. Foxp3+CD4+CD25+ regulatory T cells were not affected; however, the percentage of myeloid-derived suppressor cells (MDSC) was significantly
increased in the peripheral blood and spleen. T cell proliferation as determined by carboxyfluorescein succinimidyl ester
labeling experiments in vitro was inhibited by alcohol consumption relative to control water-drinking melanoma-bearing mice.
Collectively, these data show that chronic alcohol consumption inhibits proliferation of memory T cells, accelerates the decay
of IFN-γ producing CD8+ T cells, and increases MDSC, all of which could be associated with melanoma progression and reduced survival. 相似文献
20.
Pang YL Zhang HG Peng JR Pang XW Yu S Xing Q Yu X Gong L Yin YH Zhang Y Chen WF 《Cancer immunology, immunotherapy : CII》2009,58(6):877-886
Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. The present study was focused
on analyzing the immune status within hepatocellular carcinoma. In contrast to the increasing number of CD4+ T cells, CD8+, CD3−CD56+, CD3+CD56+, and γδT cells were all found to be under-represented in tumor infiltrating lymphocytes. Notably, the relative abundance
of CD3+CD56+ cells appeared to be correlated with patient survival. Functional analysis demonstrated that CD4+ cells in the tumor tended to produce more IL-10 but less IFN-γ, whereas CD8+ cells showed impaired capacity for the production of both IFN-γ and perforin. Consistent with previous reports, we observed
a significant increase of Foxp3+ cells in the tumor tissue. Intriguingly, although over 90% of CD4+CD25high cells were found to be Foxp3+, the majority of Foxp3+ cells were identified in the CD4+CD25medium and CD4+CD25− subsets. In support of its role as a negative regulator, CD4+CD25high cells suppressed the proliferation of CD4+CD25− cells isolated from the same tissues in an APC dependent manner. In conclusion, the tumor microenvironment of hepatocellular
carcinoma is featured by the presence of multiple immunosuppressive factors. 相似文献