Home About us Contact
|
Home About us Contact | ||
|
|
||
Immune Escape Mechanisms (immune + escape_mechanism)
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] 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] 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] 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. [source] | ||||||||||