Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients

Ozaki, Kikumi S.; Câmara, Niels Olsen Saraiva; Galante, Nelson Zocoler; Camargo, Luís Fernando Aranha; Pacheco-Silva, Álvaro

doi:10.1016/j.intimp.2004.09.008

Cited by 29 publications

(26 citation statements)

References 10 publications

(14 reference statements)

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“…Furthermore, no recovery of CD4 memory T cells was observed in a kidney recipient for whom rapamycin failed to induce tumor regression. Transplanted patients treated with rapamycin had also better outcome with regard to cytomegalovirus infection compared to patients with standard immunosuppression, suggesting that rapamycin might enhance the immune response [77]. These observations confirm recent findings that suggest that rapamycin have dichotomous effects in immunobiology.…”

Section: Mtor and Cancer; What We Have Learned From The Use Of Rapamysupporting

confidence: 81%

Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives

Dufour

Dormond-Meuwly

Demartines

et al. 2011

Cancers

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Over the last decade, extensive studies have been made to understand the role played by the mammalian target of rapamycin (mTOR) in cancer. Knowledge in this field has been gained from discoveries in basic research as well as from observations made in patients treated with allosteric mTOR inhibitors such as rapamycin. Despite promising preclinical studies, targeting mTOR in cancer therapy has shown limited clinical benefits so far. However, recent findings have revealed the complexity of the functions of mTOR in cancer and have helped develop new strategies to improve the anticancer efficacy of mTOR inhibitors. In particular, a complex network between mTOR and other signaling pathways has been identified that influences the anticancer efficacy of mTOR inhibitors. In addition, an emerging role of mTOR in the tumor microenvironment has been suggested. In this review, we confront the major findings that have been made in the past, both in experimental settings as well as in clinical trials. We further review the strategies that have been designed to further improve the efficacy of therapies targeting mTOR.

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Section: Mtor and Cancer; What We Have Learned From The Use Of Rapamysupporting

confidence: 81%

Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives

Dufour

Dormond-Meuwly

Demartines

et al. 2011

Cancers

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“…Clinical observations published over the last decade hinted at the idea that patients treated with rapamycin demonstrated better outcomes with regard to cytomegalovirus (CMV) disease and were better able to control CMV viremia than patients treated with standard calcineurin inhibitor-based immunosuppression following transplantation (8). The authors of the study speculated that the underlying mechanism involved rapamycin-mediated attenuation of viral replication, as these viruses co-opt host machinery in order to replicate (8). Recently, however, in two studies published in Nature in 2009, Araki et al and Pearce et al .…”

Section: Impact Of Rapamycin On Cd8+ T Cell Differentiation In Responmentioning

confidence: 99%

Paradoxical Aspects of Rapamycin Immunobiology in Transplantation

Ferrer

Araki

Ford

2011

American Journal of Transplantation

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Rapamycin has long been considered an immunosuppressive agent due to its anti-proliferative effects on immune cells, and is currently used as a component of anti-rejection regimens in transplantation. Despite the large number of mechanistic and clinical studies investigating the impact of rapamycin on cell-mediated immunity, several paradoxes concerning rapamycin immunobiology remain. In particular, emerging evidence suggests that under certain circumstances rapamycin can exert immunostimulatory effects, boosting T cell responses in the face of pathogen infections and vaccines. Here, we review recent findings concerning the contradictory outcomes of rapamycin induced mTOR inhibition on CD4+ and CD8+ T cell responses in transplantation and protective immunity. These studies suggest that the conditions under which T cells are stimulated can profoundly modify the impact of rapamycin on antigen-specific T cell responses. Thus, further investigation into the cellular and molecular pathways underlying the dichotomous effects of rapamycin in transplantation is required to harness the full potential of this immunomodulatory agent to promote graft survival and maximize protective immunity.

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“…Several studies indicate that mTOR inhibitors have an anti-CMV effect. 13,15,16 In a recent meta-analysis, it is suggested that CMV prophylaxis may be dispensable with the use of mTOR inhibitors with or without calcineurin inhibitors. 17 Another meta-analysis of mTOR inhibitors or mycophenolic acid with a calcineurin inhibitor as the primary immunosuppression regimen showed that mTOR reduced the risk of CMV infection by 57%.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8][9] Several studies have shown that mammalian target of rapamycin (mTOR) inhibitors can lower the risk of cardiovascular disease, 10,11 malignancy, 12 and CMV infection 13 and therefore represent an attractive option for the elderly. Thus, the aim of this study was to assess CMV infection incidence and kidney transplant outcomes in elderly recipients treated with mTOR inhibitor sirolimus-tacrolimus at low doses compared with those receiving tacrolimusmycophenolate sodium.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Kojima

Nga²,

Takase³

et al. 2018

Exp Clin Transplant

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Objectives: There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. Materials and Methods: In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimusmycophenolate (23 patients). Cytomegalovirus infec tion rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Results: Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. Conclusions: The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

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Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients

Cited by 29 publications

References 10 publications

Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives

Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives

Paradoxical Aspects of Rapamycin Immunobiology in Transplantation

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