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Escape Mechanisms (escape + mechanism)
Kinds of Escape Mechanisms Selected AbstractsCD95L mediates tumor counterattack in vitro but induces neutrophil-independent tumor rejection in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Frederik H. Igney Abstract Many tumors express CD95L (CD178, FasL, APO-1L) and may thus kill tumor-infiltrating lymphocytes, a phenomenon called tumor counterattack. However, presently it is not clear whether tumor counterattack is a relevant immune escape mechanism. To characterize the effect of CD95L expression of tumor cells on tumor-specific T cells, we established an in vitro system with TCR tg T cells and a model tumor antigen. Preactivated antitumor T cells were able to kill CD95L, and CD95L+ tumor cells. CD95L+ tumor cells killed activated T cells in vitro and inhibited the expansion of cytotoxic antitumor T cells in mixed lymphocyte tumor reactions. In vivo CD95L expression led to delayed tumor growth or complete tumor rejection. Neutrophils were not responsible for the delayed growth of the CD95L+ tumors tested. In mice with neutrophils deficient for important cytotoxicity mechanisms (p47phox,/, or iNOS,/, mice), CD95L+ tumors grew similarly as in wild-type mice. Incidence and growth rate of CD95L+ tumors in mice injected with a neutrophil-depleting or an isotype control antibody was the same. In CD95-deficient lpr mice, tumor growth was not altered as compared to wild-type mice. Taken together, CD95L mediated tumor counterattack in vitro, but led to neutrophil-independent tumor rejection in vivo. [source] Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism,CANCER, Issue 5 2006Ramy Ibrahim M.D. Abstract BACKGROUND To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them. METHODS The authors tested the expression of FASL on the surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify apoptotic cells. An in vitro functional assay was then done to test if the FASL expressed on the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues. RESULTS Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of FasL in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS The findings of the current study support the authors' hypothesis that persistent expression of FasL plays a role in the ability of cervical carcinoma cells to escape from the immune system. Cancer 2006. Published 2006 by the American Cancer Society. [source] Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyteCELLULAR MICROBIOLOGY, Issue 8 2007Maria Cristina Gagliardi Summary We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb,monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses. [source] New approaches in the immunotherapy of haematological malignanciesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Régis T. Costello Abstract: Advances in the management of haematological malignancies have allowed to obtain improved remission rates. Nonetheless, relapses impair these results and justify the search for novel therapeutic strategies. Clinical data demonstrate that the immune system plays an important role in the control of haematological malignancies. An increased frequency of haematological malignancies is observed in immunodeficiency states. Reversal of the immunosuppression is sometimes sufficient to induce tumour regression (withdrawal of cyclosporine in post-transplant lymphoproliferations, highly active anti-retroviral treatment in human immunodeficiency virus related Kaposi's disease). Another line of evidence for the involvement of the immune system in the anti-tumour response comes from the observation of spontaneous anti-tumour responses that parallel the occurrence of paraneoplastic immune-mediated syndromes. Finally, the efficiency of allogeneic transplantation in the haematological field has been clearly demonstrated to depend on the immune-mediated graft vs. leukaemia effect. Nonetheless, tumours develop in immune competent patients because of various tumour escape mechanisms, such as loss of human leucocyte antigen class I antigens, absence of target recognition by deficient adhesion/co-stimulatory molecule expression, tumour cell counterattack against immune effectors, direct (contact-dependent) or indirect (cytokine-mediated) impairment of T-lymphocyte activation. Novel immunotherapy approaches are now orientated in a convergent direction, i.e. the reversal of immune escape mechanisms either via the correction of deficient phases of the immune response or by the amplification of physiological mechanisms. [source] Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal diseaseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Francesca Avogadri Abstract Salmonella typhimurium is a facultative anaerobic bacterium able to multiply preferentially in tumors and inhibit their growth. The mechanisms through which Salmonella exerts its anti-cancer properties are not fully understood. We recently showed that intra-tumoral Salmonella injection results not only in the regression of even bulky tumor masses, but also impacts on the growth of distant untreated lesions. Here we describe how Salmonella exerts its systemic anti-cancer effects and means to potentiate them. The outburst of an early inflammatory reaction in the treated tumor promotes the development of an immunostimulatory cytokine environment both locally and in the draining lymph node. Within the next 10,days, an efficient cross-presentation of endogenous tumor antigens by dendritic cells at the tumor-draining lymph node leads to the priming of effective anti-tumor CD8+ T cell responses. This potentially broadly reactive T cell repertoire can be directed to other pre-established melanomas by low-dose radiotherapy enhancing the Salmonella anti-cancer effect. We demonstrate that Salmonella -based therapy coupled to low-dose radiotherapy dampens tumor immune escape mechanisms at different levels and allows controlling systemic disease in a CD8+ T cell-dependent manner. [source] Viral escape mechanisms , escapology taught by virusesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2001Michaela Lucas Viruses have ,studied' immunology over millions of years of coevolution with their hosts. During this ongoing education they have developed countless mechanisms to escape from the host's immune system. To illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV).LCMV is a fast replicating small RNA virus with a genome prone to mutations. Therefore, LCMV escapes from the immune system mainly by two strategies: ,speed' and ,shape change'. At the opposite extreme, MCMV is a large, complex DNA virus with a more rigid genome and thus the strategies used by LCMV are no option. However, MCMV has the coding capacity for additional genes which interfere specifically with the immune response of the host. These escape strategies have been described as ,camouflage' and ,sabotage'. Using these simple concepts we describe the spectrum of viral escapology, giving credit not only to the researchers who uncovered this fascinating area of immunology but also to the viruses themselves, who still have a few lessons to teach. [source] Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulationMEDICINAL RESEARCH REVIEWS, Issue 2 2005Jindrich Cinatl Jr. Abstract It has been known for a long time that cytomegalovirus (CMV) has evolved mechanisms that allow the escape from the host immune surveillance. In the past, many efforts have been done to elucidate the molecular mechanisms underlying this virus-mediated immune escape and thus virus persistence. However, it is unknown, whether CMV may also impair immune responses directed against tumor cells. This might have severe consequences on tumor progression and may explain the growing evidence for CMV-mediated oncomodulation. This review summarizes recent work on CMV-mediated immune escape mechanisms of tumor cells and oncomodulation and proposes novel aspects that may be important for understanding the CMV-associated tumor progression. © 2004 Wiley Periodicals, Inc. [source] Denial in cancer patients, an explorative reviewPSYCHO-ONCOLOGY, Issue 1 2007M. S. Vos Abstract Denial is a clinically relevant concept in cancer patients. It has been investigated and discussed extensively. Its definition, however, has been subject to different theoretical trends over time. From a psychoanalytical viewpoint, denial is a pathological, ineffective defence mechanism. On the other hand, according to the stress and coping model denial can be seen as an adaptive strategy to protect against overwhelming events and feelings. In this explorative review the different concepts and the prevalence of denial in cancer patients are described. The relationship between denial and background characteristics and the influence of denial on quality of life are reviewed also. The prevalence of denial of diagnosis in cancer patients ranged from 4 to 47%, denial of impact occurred 8,70% and denial of affect in 18,42% of patients. Elderly cancer patients were more likely to deny. Cultural background seemed to play a role in the prevalence of denial. Neither type of cancer nor gender seemed to be related to denial. At the most, men might be more likely to deny during the terminal phase. In a limited number of longitudinal studies, a gradual reduction in denial was found over the course of the illness. The effect of denial on physical and social functioning remained unclear while the effect on psychological functioning seemed to depend on the concept of denial used. Distractive strategies were found to reduce distress, whereas passive escape mechanisms turned out to decrease psychological well-being. Future research on the prevalence and the (mal)adaptive properties of denial in cancer patients has to be based on a clear concept, longitudinal designs and careful recording of background variables. Copyright © 2006 John Wiley & Sons, Ltd. [source] Detection of orientation-specific anti-gp120 antibodies by a new N-glycanase protection assayAPMIS, Issue 2 2002G. J. Gram Several functions have been assigned to the extensive glycosylation of HIV-1 envelope glycoprotein gp120, especially immune escape mechanisms, but the intramolecular interactions between gp120 and its carbohydrate complement are not well understood. To analyse this phenomenon we established a new microwell deglycosylation assay for determining N-linked glycan accessibility after binding of gp120-specific agents. Orientation-specific exposition of gp120 in ELISA microplates was achieved by catching with either anti-C5 antibody D7324 or anti-V3 antibody NEA-9205. We found that soluble CD4 inhibited the deglycosylation of gp120 only when gp120 was caught by D7324 and not by NEA9205. In contrast, antibodies from HIV-infected individuals inhibited the deglycosylation best when gp120 was caught by NEA9205. These results demonstrated that both the CD4-binding site and the epitopes recognised by antibodies from HIV-infected individuals have N-glycans in the close vicinity. However, the difference in gp120 orientation indicates that antibodies in HIV-infected individuals, at least partly, bind to epitopes different from the CD4-binding site. Finally, we determined the structural class of the glycan of one V1 glycosylation site of prototype HIV-1 LAI gp120, which remained unsolved from previous studies, and found that it belonged to the complex type of glycans. [source] Immune escape and exploitation strategies of cytomegaloviruses: impact on and imitation of the major histocompatibility systemCELLULAR MICROBIOLOGY, Issue 8 2004Edward S. Mocarski Jr Summary Cytomegalovirus (CMV) has yielded many insights into immune escape mechanisms. Both human and mouse CMV encode a diverse array of gene products, many of which appear to modulate the immune response in the host. Some deflect the host response to infection and contribute to lifelong viral persistence while others exploit immune cells that respond to infection. Here, the viral functions that modulate and mimic host major histocompatibility complex (MHC) function will be reviewed. Viral gene products related to both classical and non-classical components of the MHC system assure the virus will persist in immunocompetent individuals. Examples of host countermeasures that neutralize viral immunomodulatory functions have emerged in the characterization of viral functions that contribute to this stand-off in CMVs that infect humans, other primates and rodents. CMV-induced disease occurs when the immune system is not yet developed, such as in the developing fetus, or when it is compromised, such as in allograft transplant recipients, suggesting that the balance between virus escape and host control is central to pathogenesis. Although evidence supports the dominant role of immune escape in CMV pathogenesis and persistence, MHC-related immunomodulatory functions have been ascribed only subtle impact on pathogenesis and the immune response during natural infection. Viral gene products that interface with the MHC system may impact natural killer cell function, antigen presentation, and T lymphocyte immune surveillance. Many also interact with other cells, particularly those in the myeloid lineage, with consequences that have not been explored. Overall, the virus-encoded modulatory functions that have been acquired by CMV likely ensure survival and adaptation to the wide range of mammalian host species in which they are found. 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