Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy

Krystufkova, E.; Sekerkova, Alena; Striz, Ilja; Brabcova, Irena; Girmanova, Eva; Viklický, Ondřej

doi:10.1093/ndt/gfr693

Cited by 61 publications

(41 citation statements)

References 25 publications

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“…A negative prognostic impact of tumor-infiltrating regulatory T cells has been shown for several types of cancer, including gastric cancer. [46][47][48][49][50][51][52][53] The comprehensive mutational analysis in this study is in concordance with the findings of other studies. 54 That we could not find a correlation between the genomic profile and expression of immune checkpoint receptors is probably due to the low frequencies of the analyzed mutations.…”

Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted nextgeneration sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumordraining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/ 127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.Abbreviations: CTLA-4, cytotoxic T lymphocyte associated molecule 4; PBMC, peripheral blood mononuclear cells; PD-1, programmed death 1; PD-L1, programmed death 1 ligand 1; TDLN, tumor-draining lymph nodes; UICC, Union International Contre le Cancer.

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Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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“…Tregs. [24][25][26] Taking into account the potential impacts of basiliximab on Treg function and the well-accepted fact that a complex network of cytokines, cellular receptors, and immune cell subsets resulting in the initiation and maintenance of aGVHD, we speculated that the blockade of multiple effector pathways may ultimately be necessary. To our knowledge, our study is the first prospective, multi-center clinical trial to develop a combined inflammatory cytokine inhibition therapy for SRaGVHD by using basiliximab and etanercept.…”

Section: Discussionmentioning

confidence: 99%

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p D 0.043, RR D 3.169), development of grades III-IV liver aGVHD (p D 0.007, RR D 5.034) and cytomegalovirus (CMV) reactivation (p D 0.035, RR D 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

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“…A few relevant investigations suggest that depletion of alloimmune responsive CD4, CD8 cells along with up-regulation of peripheral tolerance through generation of Treg cells is a therapeutic approach for treatment of RRMS and organ transplant. [24][25][26] The mean time of reconstitution of CD19, CD8, and CD4 was found 6, 10, and 36 months after alemtuzumab treatment. 24 Different investigators also suggest a combination of alemtuzumab and T cell depleting antibody (antithymocyte globulin) as a low-risk steroid-free treatment strategy for kidney transplant.…”

Section: Alemtuzumab As Immunomodifier In Transplant Therapymentioning

confidence: 96%

“…Alemtuzumab (commercially known as CAMPATH or Lemtrada) is a humanized monoclonal antibody raised against CD52, a membrane bound cell surface marker (21)(22)(23)(24)(25)(26)(27)(28) found primarily on B and T lymphocytes. The abundance of CD52 is small to moderate in macrophages, monocytes, and natural killer cells.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2016

Exp Clin Transplant

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Successful attenuation of allograft rejection rate is a major clinical aspect in transplant. The CD52 binding monoclonal antibody CAMPATH1 or alemtuzumab, in this aspect, shows a promise as an effective immunomodifier. This humanized monoclonal antibody efficiently depletes CD52-bearing mature B-and T lymphocytes from circulation and thereby causes transient lymphopenia, a condition for generalized immunosuppression. Alemtuzumab is an approved drug for the treatment of B cell chronic lymphocytic leukemia. However, its implication in transplant as nonsteroidal drug is a growing area of investigation. Here, we provided a brief account on alemtuzumab as an immunomodifier in allotransplant.

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Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy

Abstract: In this study, the rATG induction therapy was associated with an expansion of regulatory cells. Sustained high CD4(+)FoxP3(+)/Teff ratios were associated with the absence of rejection after basiliximab induction.

Cited by 61 publications

References 25 publications

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

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