The mosaic of immunosuppressive drugs

Masri, Marwan

doi:10.1016/s0161-5890(03)00075-0

Cited by 50 publications

(43 citation statements)

References 37 publications

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“…Note that rapamycin is known to block interleukin-2 activation, important for T-cell activation in effective anti-tumor responses. 34 Potentially negative interactions with rapamycin treatment, a known immunosuppressant, should thus be considered when treating LAM with existing melanoma vaccines.…”

Section: Discussionmentioning

confidence: 99%

Melanoma-Associated Antigen Expression in Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to Cytotoxic T Cells

Klarquist

Barfuss

Kandala

et al. 2009

The American Journal of Pathology

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The antibody HMB45 is used to diagnose lymphangioleiomyomatosis, a hyperproliferative disorder of lung smooth muscle cells with mutations in both alleles of either TSC1 or TSC2. A subset of these tumor cells expresses the melanoma-associated antigens gp100 and melanoma antigen recognized by T cells (MART-1). To explore the feasibility of targeting tumors in lymphangioleiomyomatosis by melanoma immunotherapy, we therefore assessed melanoma target antigen expression and existing immune infiltration of affected tissue compared with normal lung and melanoma as well as the susceptibility of cultured lymphangioleiomyomatosis cells to melanoma reactive cytotoxic T lymphocytes in vitro. Tumors expressed tyrosinase-related proteins 1 and 2 but not tyrosinase, in addition to gp100 and MART-1, and were densely infiltrated by macrophages, but not dendritic cells or T cell subsets. Although CD8 ؉ lymphocytes were sparse compared with melanoma, cells cultured from lymphangioleiomyomatosis tissue were susceptible to cytotoxic, gp100 reactive, and major histocompatibility complex class I restricted CD8 ؉ T cells in functional assays. Responder T cells selectively clustered and secreted interferon-␥ in response to HLA-matched melanocytes and cultured lymphangioleiomyomatosis cells. This reactivity exceeded that based on detectable gp100 expression; thus , tumor cells in lymphangioleiomyomatosis may process melanosomal antigens different from melanocytic cells. Therefore , boosting immune responses to gp100 in lymphangioleiomyomatosis may offer a highly desirable treatment option for this condition.

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Section: Discussionmentioning

confidence: 99%

Melanoma-Associated Antigen Expression in Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to Cytotoxic T Cells

Klarquist

Barfuss

Kandala

et al. 2009

The American Journal of Pathology

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“…16 Rag2, and Il2rg genes 10 were used to determine genotypes of offspring. Animals were maintained with drinking water containing NTBC at a concentration of 7.5 g/ml.…”

Section: Rag2mentioning

confidence: 99%

Liver Xeno-Repopulation with Human Hepatocytes in Fah−/−Rag2−/− Mice after Pharmacological Immunosuppression

Zhang

et al. 2010

The American Journal of Pathology

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Functional human hepatocytes xeno-engrafted in mouse liver can be used as a model system to study hepatitis virus infection and vaccine efficacy. Significant liver xeno-repopulation has been reported in two kinds of genetically modified mice that have both immune deficiency and liver injury-induced donor hepatocyte selection: the uPA/SCID mice and Fah ؊/؊ Rag2؊/؊ Il2rg ؊/؊ mice. The lack of hardy breeding and the overly elaborated technique in these two models may hinder the potential future application of these models to hepatitis virus infection and vaccination studies. Improving the transplantation protocol for liver xeno-repopulation from human hepatocytes will increase the model efficiency and application. In this study, we successfully apply immunosuppressive drug treatments of anti-asialo GM1 and FK506 in

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“…Blockade of IL-2 signaling has long been recognized as a route to achieving immune suppression and prolonging graft survival (Kirkman et al 1985;Reed et al 1989;Masri 2003). Prior to the discovery of therapeutic antibodies, IL-2 signaling was prevented by corticosteroids, cyclosporine (via calcineurin inhibition), and rapamycin (through the mTOR pathway) (Hardinger et al 2004;Ponticelli 2005;Geissler et al 2008).…”

Section: Allograft Transplantationmentioning

confidence: 99%