共查询到20条相似文献,搜索用时 15 毫秒
1.
Alexei F. Kirkin P. thor Straten J. Zeuthen 《Cancer immunology, immunotherapy : CII》1996,42(4):203-212
Human melanoma is a highly immunogenic tumor capable of inducing a specific immune response. A number of melanoma-associated
antigens have been characterized during the past several years and can be classified into two groups: differentiation antigens
– present also in normal melanocytes – and tumor-specific antigens, which, with the exception of testis, are present only
in tumor cells. In a previous publication [Kirkin A. F., Petersen T. R., Olsen A. C., Li L., thor Straten P., Zeuthen J. (1995)
Cancer Immunol Immunother 41:71] we have described the production of clones of cytotoxic T lymphocytes (CTL) against the highly
immunogenic human melanoma cell line FM3. Using these clones we have defined four previously unknown melanoma-associated antigens,
which could be subdivided into differentiation and progression antigens. In the experiments reported in this paper, we have
further compared CTL clones from different groups and shown that the sensitivity of melanoma cells to CTL that recognize differentiation
or progression antigens is differentially modulated during tumor progression as well as by the lymphokines interferon γ (IFNγ)
and interleukin-10 (IL-10). The interaction of CTL clones recognizing progression antigens was strongly increased after treatment
of melanoma cells with IFNγ, while the recognition by CTL clones specific for differentiation antigens either was unchanged
or significantly decreased. IL-10 treatment of melanoma cells induced up-regulation with respect to recognition by CTL clones
specific for differentiation antigens without affecting the recognition of melanoma cells by CTL clones specific for progression
antigens. Using cellular systems at different stages of tumor progression, we demonstrated that the progressed state of melanoma
cells is associated with increased sensitivity to recognition by CTL clones detecting progression antigens, and with decreased
sensitivity to CTL clones recognizing differentiation antigens. Mimicking tumor progression, treatment with IFN-γ induced
apparent down-regulation of differentiation antigens. A hypothesis is suggested in which IFN-γ plays different roles in the
immune response against poorly immunogenic and highly immunogenic melanoma cells, increasing the progression of poorly immunogenic
tumor cells or promoting a strong immune response and regression of highly immunogenic melanoma cells.
Received: 23 November 1995 / Accepted: 7 March 1996 相似文献
2.
In situ T cells in melanoma 总被引:3,自引:0,他引:3
Per thor Straten Jürgen C. Becker Per Guldberg Jesper Zeuthen 《Cancer immunology, immunotherapy : CII》1999,48(7):386-395
During the past decade new insights have been gained into the role of T lymphocytes in the host's immune response to cancer
in general and to melanoma in particular. Several melanoma-associated antigens (MAA) recognized by T cells have been characterized,
and a number of HLA class I- and class II-restricted peptides have been identified. These antigens can be divided into three
different groups: tumor-associated testis-specific antigens, melanocyte differentiation antigens, and mutated or aberrantly
expressed antigens. These proteins give rise to several antigenic peptides. The number of known melanoma-associated peptides
that can induce killing by cytotoxic T-lymphocytes (CTL) exceeds 30 and is still increasing. In line with these findings,
clinical data indicate that the immune system is essential in the control of tumor growth. A brisk infiltration of lymphocytes
is associated with a favorable prognosis, and complete or partial regression of primary melanoma occurs quite frequently.
Furthermore, immunomodulatory therapies have accomplished complete or partial tumor regression in a number of patients. However,
the immune response is in most cases inadequate to control tumor growth as tumor progression often occurs. Hence, the coexistence
of a cellular immune response in melanoma lesions, demonstrated by the presence of clonally expanded T cells, remains a major
paradox of tumor immunology. In the present paper we review current knowledge regarding tumor infiltrating lymphocytes (TIL)
in melanoma and discuss possible mechanisms of escape from immune surveillance.
Received: 20 March 1999 / Accepted: 3 March 1999 相似文献
3.
Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines 总被引:8,自引:0,他引:8
Arenberg DA Keane MP DiGiovine B Kunkel SL Strom SR Burdick MD Iannettoni MD Strieter RM 《Cancer immunology, immunotherapy : CII》2000,49(2):63-70
Bronchogenic carcinoma is the leading cause of malignancy-related mortality in the United States, with an overall 5-year
survival rate of less than 15%. This aggressive behavior reflects, among other traits, the capacity of the tumor to evade
normal host immune defenses, and to induce a pro-angiogenic environment. A central feature of any immune response toward tumors
is the recruitment of specific immune cell populations. In the present study we investigated the infiltration of monocytes
in human specimens of non-small-cell lung cancer (NSCLC). The presence of macrophages in NSCLC tumors was documented by immunohistochemistry.
In vitro chemotaxis assays demonstrated higher monocyte chemotactic activity in NSCLC tumor homogenates than in normal lung
tissue. We next investigated the expression of CC chemokines within specimens of NSCLC tumors. Levels of the CC chemokines
were higher in NSCLC tumor tissue than in normal lung tissue. Immunolocalization showed that the cells associated with antigenic
CC chemokines were the malignant tumor cells, as well as occasional stromal cells. Maximal inhibition of monocyte chemotaxis
induced by NSCLC in vitro occurred in the presence of neutralizing antibodies to MCP-1 and MIP-1β. On follow-up of 15 patients
in whom we quantified macrophage infiltration, we found that those with recurrence of disease had higher levels of macrophage
infiltration in their initial tumors. However, the functional significance of CC-chemokine-mediated macrophage infiltration
into NSCLC remains to be determined.
Received: 12 November 1999 / Accepted: 10 December 1999 相似文献
4.
Craig L. Slingluff 《Cancer immunology, immunotherapy : CII》1999,48(7):371-373
Cytotoxic T-cell responses to shared tumor antigens have been characterized for several tumor types, and the MHC-associated
peptides that comprise these antigens have been defined at a molecular level. These provide new tools to determine whether
immune responses can be generated with these tumor antigens, and there are data to suggest that such immune responses can
be generated. However, it is also clear that tumor cells can evade immune responses directed against some shared antigens,
by downregulating expression of MHC or of the antigenic protein(s), as well as by more active methods such as secretion of
immunosuppressive cytokines. Awareness of these mechanisms of immune escape will help to direct development of the next generation
of tumor vaccines. Targeting unique antigens and modulating the cytokine environment likely will be critical to comprehensive
vaccine systems in the future.
Received: 20 March 1999 / Accepted: 3 May 1999 相似文献
5.
Julie A. McEarchern David G. Besselsen Emmanuel T. Akporiaye 《Cancer immunology, immunotherapy : CII》1999,48(2-3):63-70
Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that contributes to the immunological escape of tumor
cells. In a previous study we demonstrated that inhibition of TGFβ production by EMT6 murine mammary tumor cells expressing
an antisense TGF-β transgene reduces their tumorigenicity. On the basis of this observation we hypothesized that down-regulation
of TGFβ production coupled with interferon γ (IFNγ) stimulation would induce an immune response superior to that generated
by either strategy alone. In this study, EMT6 tumor cells expressing antisense TGFβ were transduced with the murine IFNγ gene.
Tumor cells expressing either or both transgenes grew more slowly than mock-transduced tumors. Dual-transgene-expressing tumor
cells were more immunogenic than tumor cells expressing either transgene alone. Studies in mice depleted of T cell subsets
indicated that CD8+ T cells are the primary effectors of the antitumor activity observed. These results suggest that down-regulation of immunosuppression
combined with cytokine-mediated immune augmentation is a useful strategy to improve antitumor immunity.
Received: 6 October 1998 / Accepted: 15 January 1999 相似文献
6.
7.
Nafiseh Pakravan Ladan Langroudi Monire Hajimoradi Zuhair Mohammad Hassan 《Cell stress & chaperones》2010,15(6):977-984
Heat-shock proteins have biochemical and immunological roles in chaperoning/signaling and activation of innate and adaptive
immune responses, respectively. Their effect on the immune response is due to a phenomenon known as cross-priming of antigen,
in which exogenous antigens are presented via MHC class I by antigen presenting cells. GP96 exerts adjuvant activity with
some viral and bacterial antigens when applied in the form of a DNA vaccine. In this study, animals with Her2-expressing tumors
were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines. Analyses of the immune response, 2 weeks after the last
immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased
IFN-γ/IL-4 level. Nevertheless, the graph of tumor size demonstrated a bi-phasic pattern in which partial control of tumor
progression initially occurred, but finally its effectiveness was inversely affected by tumor size. 相似文献
8.
Merchant MS Melchionda F Sinha M Khanna C Helman L Mackall CL 《Cancer immunology, immunotherapy : CII》2007,56(7):1037-1046
Primary tumors developing in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This
raises the prospect that metastases derived from such tumors will also evade immunity. To investigate whether immune surveillance
plays a role in preventing metastases, we studied a murine model which mimics the clinical progression of osteosarcoma: primary
tumor growth in the lower extremity, amputation, minimal residual disease followed by the development of overt metastases.
K7M2 implants readily escaped immune surveillance since normal BALB/c mice, T cell deficient SCID and T/NK cell deficient
SCID-bg mice showed no difference in the rate of growth of primary osteosarcomas. However, both SCID and SCID-bg mice had
higher rates of metastases than immunocompetent mice. Similarly, immune reconstitution following transfer of naive T cells
to SCID or SCID-bg mice did not impact primary tumor growth, but significantly diminished metastatic recurrence. T cells in
osteosarcoma bearing mice produced IFNγ in response to tumor and IFNγ production by immune reconstituting T cells was required
to prevent metastases. These results demonstrate an important role for T cell based immune surveillance in preventing metastases,
even when metastases develop from tumors that adeptly evade immunosurveillance. The results further suggest that T cell depleting
cancer therapies may eliminate beneficial immune responses and that immune reconstitution of lymphopenic cancer patients could
prevent metastatic recurrence of solid tumors.
By acceptance of this article, the publisher or recipient acknowledges right of the U.S. Government to retain a nonexclusive,
royalty-free license in and to any copyright covering the article.
The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Animal care
was provided in accordance with procedures outlined in the “Guide for the Care and Use of Laboratory Animals” (NIH Pub. No.
86-23, 1996). This project was funded in whole or part with funds from the National Cancer Institute, National Institutes
of Health, under Contract No. NO1-CO-56000. 相似文献
9.
Waltraud Böhm Reinhold Schirmbeck J. Reimann 《Cancer immunology, immunotherapy : CII》1997,44(4):230-238
We demonstrate in a murine model that targeting an anti-viral T cell response to a growing tumor facilitates priming of a
tumor-associated antigen (TAA)-specific, rejecting T cell response. Murine P815 mastocytoma cells grow aggressively in a syngeneic
host. Transfected P815/S cells (expressing the hepatitis B surface antigen, HBsAg) also grow as subcutaneous tumors, but occasional
‘spontaneous’ rejections after transient growth are observed. Growth of P815/S tumors (but not of P815 tumors) is efficiently
suppressed by a CD8+ cytotoxic T lymphocyte (CTL)-dependent immune mechanism in mice primed to HBsAg by DNA–immunization. In hosts immunized against
HBsAg by DNA vaccination, HBsAg-specific CTL are generated. This specific CTL reactivity was targeted to s.c.-growing P815
tumors by intra tumor injections of either HBsAg-encoding plasmid DNA or viable P815/S cells; this treatment led to tumor
rejection in 70–80% of the tumor-bearing animals. All rejecting animals showed a CD8+ CTL-dependent resistance to subsequent challenges by native, non-transfected P815 tumors. Targeting an established anti-viral
(‘strong’) CTL response to a growing tumor hence is an efficient strategy to facilitate priming of a rejecting CTL response
against (‘weak’) TAA in this system.
Received: 18 December 1996 / Accepted: 6 February 1997 相似文献
10.
Keith R. Jerome Allan D. Kirk Gabriele Pecher Wayne W. Ferguson O. J. Finn 《Cancer immunology, immunotherapy : CII》1997,43(6):355-360
The human mucin, MUC-1, is a transmembrane glycoprotein that is produced by both normal an malignant epithelium. The MUC-1
produced by malignant epithelium is underglycosylated, which leads to the expression by tumors of novel T and B cell epitopes
on the mucin polypeptide core. Similar underglycosylation occurs in the lactating breast. In this report, we describe a long-term
survivor of breast cancer whose tumor strongly expressed the T- and B-cell-stimulatory epitopes. Five years after presenting
with the tumor, the patient had her first pregnancy, at which time she developed fulminant lymphocytic mastitis. We demonstrate
that the lactating breast produced mucin expressing the same “tumor-specific” epitopes as the original cancer. The patient
had circulating anti-mucin antibodies of both the IgM and IgG isotypes (these are not found in normal controls), and mucin-specific
cytotoxic T lymphocytes in the peripheral blood. Limiting – dilution analysis for mucin – specific cytotoxic T lymphocytes
in three different experiments yielded frequencies of 1 in 3086, 1 in 673, and 1 in 583, compared to approximately 1 in 106 in normal controls. The patient remains clinically free of carcinoma after 5 additional years of follow-up. We propose that
the original tumor primed the patient’s immune response against the mucin epitopes, and that the re-expression of these epitopes
on the lactating breast evoked a secondary immune response. It is tempting to speculate that the vigor of her anti-mucin immunity
may have helped protect this patient against recurrent tumor.
Received: 12 February 1996 / Accepted: 5 November 1996 相似文献
11.
Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines derived from the same patient 总被引:2,自引:0,他引:2
Real LM Jimenez P Kirkin A Serrano A García A Cantón J Zeuthen J Garrido F Ruiz-Cabello F 《Cancer immunology, immunotherapy : CII》2001,49(11):621-628
Progressive tumor growth may be associated with suppression of the immune response. Many different mechanisms may contribute
to immune evasion. We investigated some of these mechanisms in melanoma cells lines generated from two patients. These cell
lines show a complex pattern of altered HLA expression; however, the resulting phenotype did not satisfactorily explain the
simultaneous evasion of T and NK cell cytotoxicity. Two additional alterations have now been detected in these melanoma cell
lines: (1) resistance to FAS-induced apoptosis caused by defective FAS gene expression, and (2) constitutive expression of
immunosuppressive cytokines. Our results show that several of the major mechanisms for immune evasion may coexist in a single
tumor. This suggests that tumor progression may give rise to an extremely resistant phenotype, which may be an impediment
to some immunotherapeutic strategies. We hypothesize that the simultaneous presence of several mechanisms involved in tumor
immune evasion must be the result of progressive selection of characteristics that are advantageous for tumor survival in
a competent host. Our findings do not support the possibility that FASL expression is a common mechanism of evasion of immune
response in melanoma cells.
Received: 27 January 2000 / Accepted: 28 August 2000 相似文献
12.
Chungwen Wei Eugene Storozynsky A. J. McAdam Kun-Yun Yeh Brian R. Tilton Richard A. Willis Richard K. Barth R. John Looney Edith M. Lord J. G. Frelinger 《Cancer immunology, immunotherapy : CII》1996,42(6):362-368
Human prostate-specific antigen (PSA) has a highly restricted tissue distribution. Its expression is essentially limited
to the epithelial cells of the prostate gland. Moreover, it continues to be synthesized by prostate carcinoma cells. This
makes PSA an attractive candidate for use as a target antigen in the immunotherapy of prostate cancer. As a first step in
characterizing the specific immune response to PSA and its potential use as a tumor-rejection antigen, we have incorporated
PSA into a well-established mouse tumor model. Line 1, a mouse lung carcinoma, and P815, a mouse mastocytoma, have been transfected
with the cDNA for human PSA. Immunization with a PSA-expressing tumor cell line demonstrated a memory response to PSA which
protected against subsequent challenge with PSA-expressing, but not wild-type, tumors. Tumor-infiltrating lymphocytes could
be isolated from PSA-expressing tumors grown in naive hosts and were specifically cytotoxic against a syngeneic cell line
that expressed PSA. Immunization with tumor cells resulted in the generation of primary and memory cytotoxic T lymphocytes
(CTL) specific for PSA. The isolation of PSA-specific CTL clones from immunized animals further demonstrated that PSA can
serve as a target antigen for antitumor CTL. The immunogenicity studies carried out in this mouse tumor model provide a rationale
for the design of methods to elicit PSA-specific cell-mediated immunity in humans.
Received: 4 April 1996 / Accepted: 31 May 1996 相似文献
13.
Wolfgang H. Fischer Per thor Straten Patrick Terheyden Jürgen C. Becker 《Cancer immunology, immunotherapy : CII》1999,48(7):363-370
A major difficulty for tumor immunotherapy derives from the phenomenon that the encounter of the immune system with an antigen
does not necessarily result in activation, but may also be followed by the induction of tolerance either by anergy or physical
deletion. It is well established that the immune system becomes alerted only in the face of danger, i.e. upon ligand recognition
in the context of increased expression of costimulatory molecules, adhesion molecules, and MHC molecules on antigen-presenting
cells (APC). The pivotal role of CD4+ T lymphocytes in this process has been established. However, encounter of CD4+ T cells with either MHC class II-expressing melanoma cells or certain tumor antigen-presenting APC has been reported to induce
antigen-specific tolerance. Thus, as more is learned about the molecular regulation of immune responses and the role of CD4+ T cells in particular, additional strategies to block inhibitory pathways of T-cell activation will be developed. Such strategies
are likely to be based on a modulation of the context in which antigen is encountered by the immune system, e.g. in situ cytokine
therapy, induction of costimulatory molecules or the simulation of `danger' signals.
Received: 20 March 1999 / Accepted: 3 May 1999 相似文献
14.
Tanigawa K Yu H Sun R Nickoloff BJ Chang AE 《Cancer immunology, immunotherapy : CII》2000,48(11):635-643
We utilized the gene gun to transfect subcutaneous D5 melanoma and MT-901 mammary carcinoma tumors in situ with a granulocyte/macrophage-colony-stimulating
factor (GM-CSF) plasmid complexed to gold particles. There was diminished tumor growth following bombardment with GM-CSF plasmid,
which was apparent only during the period of administration. Transgenic GM-CSF was produced by the skin overlying the tumors
and not by the tumors themselves. GM-CSF plasmid bombardment resulted in increased cell yields within tumor-draining lymph
nodes (TDLN) with at least a 12-fold increase in the percentage of dendritic cells (8.9%) compared to controls (0.7%). Secondarily
activated TDLN cells from animals transfected with GM-CSF demonstrated enhanced cytokine release (interferon γ, GM-CSF and
interleukin-10) in response to tumor stimulator cells compared to controls, and had an increased capacity to mediate tumor
regression in adoptive immunotherapy. There was a small, but detectable, non-specific immune adjuvant effect observed with
gold particle bombardment alone, which was less than with GM-CSF plasmid. The adjuvant effect of GM-CSF plasmid required peri-tumoral
transgene expression since gene bombardment away from the tumor was ineffective.
Received: 27 April 1999 / Accepted: 27 August 1999 相似文献
15.
Ussama M. Abdel-Motal Kim Wigglesworth Uri Galili 《Cancer immunology, immunotherapy : CII》2009,58(10):1545-1556
α-Gal glycolipids capable of converting tumors into endogenous vaccines, have α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) and
are extracted from rabbit RBC membranes. α-Gal epitopes bind anti-Gal, the most abundant natural antibody in humans constituting
1% of immunoglobulins. α-Gal glycolipids insert into tumor cell membranes, bind anti-Gal and activate complement. The complement
cleavage peptides C5a and C3a recruit inflammatory cells and APC into the treated lesion. Anti-Gal further opsonizes the tumor
cells and targets them for effective uptake by recruited APC, via Fcγ receptors. These APC transport internalized tumor cells
to draining lymph nodes, and present immunogenic tumor antigen peptides for activation of tumor specific T cells. The present
study demonstrates the ability of α-gal glycolipids treatment to prevent development of metastases at distant sites and to
protect against tumor challenge in the treated mice. Adoptive transfer studies indicate that this protective immune response
is mediated by CD8+ T cells, activated by tumor lesions turned vaccine. This T cell activation is potent enough to overcome
the suppressive activity of Treg cells present in tumor bearing mice, however it does not elicit an autoimmune response against
antigens on normal cells. Insertion of α-gal glycolipids and subsequent binding of anti-Gal are further demonstrated with
human melanoma cells, suggesting that intratumoral injection of α-gal glycolipids is likely to elicit a protective immune
response against micrometastases also in cancer patients. 相似文献
16.
Egorov IK 《Cancer immunology, immunotherapy : CII》2006,55(1):1-22
Tumor escape from the host immune response remains the major problem holding the development of immunotherapies for cancer.
In this review, congenic mouse lines are discussed that differ dramatically in their ability to respond to tumors tested and,
thereby, to survive or to succumb to the tumor and/or its metastases. This ability is under the control of either MHC class
I or nontrivial MHC class II β genes expressed in a small subpopulation of antigen-presenting cells. Two hypotheses can explain
the results obtained so far: (1) emergence of tumor cell variants that escape the host immune response in morbid mice but
are eliminated in survivors, and (2) tumor-induced immunosuppression, which is either efficient or not, depending on the congenic
line used. It is argued that further experimentation on these congenics will allow to choose the correct hypothesis, and to
characterize the mechanism(s) of elimination of minimal residual disease and prevention of tumor escape by the immune system
of survivors as well as the reason(s) for its failure in morbid mice. It is also argued that the use of these models will
substantially increase the chance to resolve the controversy of poor correlation of immunotherapy testing in mice with clinical
results. 相似文献
17.
Relationship between immune state and tumor growth rate in rats bearing progressive and non-progressive mammary tumors 总被引:1,自引:0,他引:1
María Mónica Remedi Ernesto Hliba Marcela Demarchi Mirtha Depiante-Depaoli 《Cancer immunology, immunotherapy : CII》1998,46(6):350-354
Impaired immune responses occur frequently in cancer patients or in tumor-bearing animals, but the mechanisms of the tumor-induced
immune defects remain poorly understood. The aim of the present study was to determine the relevance of the immune system
in the control of tumor growth. We have developed a model of progressive and non-progressive mammary tumor, chemically induced
in female Wistar rats. In this model we evaluated the development of an immune response after immunization of rats bearing
progressive and non-progressive tumors with a non-related antigen, such as sheep red blood cells. We also studied the activation
state of peritoneal macrophages from animals bearing tumors by evaluating the production of free radicals. Our findings indicated
that the cell-mediated immunity in rats bearing progressive tumors fails to respond to heterologous antigen in vivo, as demonstrated
by a negative delayed-type hypersensitivity reaction, and is accompanied by minor nitric oxide production by peritoneal exudate
cells as well as a lower capacity for macrophage activation. The study of non-progressive tumor-bearing rats indicated that
the cell-mediated immune response was intact and an activated state of macrophages was found in vivo. The results described
in this paper should be taken into account when therapies based on cancer vaccines are chosen for the treatment of cancer.
Received: 26 February 1998 / 9 April 1998 相似文献
18.
Kim BG Joo HG Chung IS Chung HY Woo HJ Yun YS 《Cancer immunology, immunotherapy : CII》2000,49(8):433-440
Interleukin-10 (IL-10) has both inhibitory and stimulatory effects on diverse cell types of the immune system. It inhibits
the antigen-presenting capacity of monocytes/macrophages and stimulates T cell proliferation. Although many tumors spontaneously
release IL-10, the physiological relevance of this phenomenon to the in vivo antitumor immune response is not known. To elucidate
the physiological role of tumor-released IL-10, we used IL-10-specific antisense oligodeoxynucleotides (AS-ODN) for the inhibition
of IL-10 production from the tumor cells. Incubation of MOPC 315 plasmacytoma with IL-10 AS-ODN in vitro resulted in inhibition
of IL-10 production and also in enhancement of the expression of major histocompatibility complex (MHC) class I, MHC class
II, and B7-1 molecules. MOPC 315 cells incubated with IL-10 AS-ODN (MOPC-IL10AS) for 16 h in vitro showed reduced tumorigenicity
in Balb/c mice. The mice implanted with MOPC-IL10AS effectively rejected the tumor graft, and showed strong cytotoxic T lymphocyte
(CTL) activity against the parental MOPC 315 cells. In addition, MOPC-IL10AS were more effective as stimulator cells in mixed
lymphocyte/tumor cell culture, and as target cells in a CTL assay. These results imply that IL-10 spontaneously released from
MOPC 315 cells inhibits their immunogenicity and that the inhibition of IL-10 production by IL-10 AS-ODN may be a way to enhance
the host cellular antitumor immune response.
Received: 11 November 1999 / Accepted: 6 April 2000 相似文献
19.
Signaling defects in T lymphocytes of patients with malignancy 总被引:12,自引:0,他引:12
Theresa L. Whiteside 《Cancer immunology, immunotherapy : CII》1999,48(7):346-352
In patients with cancer, alterations in the expression of T-cell receptor-associated molecules in tumor-infiltrating lymphocytes
(TIL) as well as in circulating lymphocytes have been reported. By quantitative flow cytometry analysis, decreased or absent
expression of the ζ chain in CD4+ or CD8+ T cells as well as in natural killer (NK) cells was demonstrated in patients with malignancies. Changes in the expression
of ζ are biologically significant, because the absence or low expression of this signaling molecule in TIL of patients with
stage III or IV head and neck cancer predicts a significantly shorter 5-year survival than that of patients with normal ζ
expression in TIL. Preliminary evidence indicates that expression of ζ in TIL may not only influence survival but also predicts
a favorable response to biologic therapies. Patients with cancer also show significantly greater spontaneous ex vivo apoptosis
in peripheral blood mononuclear cells (PBMC) compared to normal controls, as measured by a terminal deoxynucleotide transferase-mediated
dUTP nick end labeling (TUNEL) assay. While no correlation could be established between the proportions of cells with low
ζ chain expression and those that spontaneously apoptose ex vivo, the ζ chain has been shown to be cleaved by caspases in
T cells coincubated with tumor cells or with T cells exposed to CH-11 antibody, which induces apoptosis upon crosslinking
Fas on the cell surface. The results suggest that low/absent ζ chain expression and lymphocyte apoptosis may be manifestations
of negative effects of the tumor on the host immune system.
Received: 20 March 1999 / Accepted: 3 May 1999 相似文献
20.
M. Margaret Prechel Yvonne Lozano Mark A. Wright J. Ihm M. R. I. Young 《Cancer immunology, immunotherapy : CII》1996,42(4):213-220
Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and increase the presence of granulocyte/macrophage (GM) progenitor
cells having natural suppressor activity. Treatment of these tumor-bearing mice with interleukin-12 (IL-12) resulted in minimal
immune modulation. The objective of this study was to determine whether eliminating natural suppressor activity would allow
for immune stimulation by IL-12. Treatment of LLC-LN7 tumor-bearing mice with vitamin D3 eliminated natural suppressor activity. In mice that were first treated with vitamin D3 and then also with IL-12, there was stimulation of splenic T cell proliferation in response to immobilized anti-CD3 plus
IL-2. In addition, spleen and lymph node cells from vitamin-D3/IL-12-treated tumor-bearing mice became stimulated in response to autologous tumor to produce interferon γ (IFNγ), although
IL-2 production was not stimulated. A prominent effect of the combined vitamin-D3/IL-12 treatment regimen was the synergistic augmentation of autologous tumor-specific cytolytic activity within the regional
lymph nodes. The generation of these tumor-specific effector cells required the presence of the tumor mass since such activity
was not elicited in the lymph nodes of mice from which the tumors had been surgically excised. The results of this study show
that, after treatment of tumor bearers with vitamin D3 to eliminate GM-suppressor cells, IL-12 can induce select regional antitumor immune responses, particularly IFNγ production
and cytolysis by regional lymph node cells of autologous tumor.
Received: 15 December 1995 / Accepted: 22 March 1996 相似文献