Resetting the T Cell Compartment in Autoimmune Diseases With Autologous Hematopoietic Stem Cell Transplantation: An Update

Lutter, Lisanne; Spierings, Julia; Rhijn-Brouwer, Femke C C van; Laar, Jacob M van; Wijk, Femke van

doi:10.3389/fimmu.2018.00767

Cited by 15 publications

(16 citation statements)

References 38 publications

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“…aHSCT is a well-established treatment for hematologic malignancies and is increasingly used for refractory autoimmune diseases to halt autoimmune destruction and reestablish tolerance ( 10 ). The putative mechanism points to greater diversity in the T-cell repertoire ( 11 ), thymus reactivation of regulatory T cells (Tregs) ( 12 ), and an increase in the function or number of Tregs ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

et al. 2020

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Immune checkpoint inhibitors (ICIs) perturb T-cell regulatory pathways to enhance antitumor immunity. However, an increase reporting of ICI-associated diabetes is observed in adults. To our knowledge, no cases have been reported in the pediatric population. RESEARCH DESIGN AND METHODS We describe a pediatric case of ICI-associated type 1 diabetes in a 12-year-old Hispanic boy with Hodgkin lymphoma. The patient had a history of autologous hematopoietic stem cell transplantation and was treated with pembrolizumab after disease progression. RESULTS The patient was admitted for diabetic ketoacidosis after five cycles of pembrolizumab. The patient was discharged with daily insulin injections and has continued on exogenous insulin ever since. CONCLUSIONS The expanded ICI use may lead to more cases in pediatric patients as has been observed in adults. Considering the acute manifestation of diabetes and the added burden of lifelong insulin therapy, in particular for pediatric patients and their families, monitoring and education of ICI-associated diabetes in children is needed. Insulin-dependent diabetes associated with immune checkpoint inhibitors (ICIs) is a rare phenomenon but of high clinical significance due to its presentation as potentially life-threatening diabetic ketoacidosis (DKA). In the setting of advanced malignancies, ICI-associated diabetes may seem peripheral, but its chronicity, complications, and daily glucose monitoring and insulin injections drastically alter patients' quality of life and complicate cancer treatment. Moreover, the unprecedented level of interest in immunotherapy research will lead to more widespread use of ICIs and a subsequent increase in diabetes, as evidenced by recent data (1-3). One study reported 283 new cases during a 4-year period, with more than half reported in 2017 (1). The primary cancer types were melanoma (43%), lung (32%), and renal (10%), indicative of early ICI approvals in these tumors. While the nature of ICI-associated diabetes is better defined for melanoma, other malignancies, such as lymphoma, are rarely reported, making it difficult to assess patient characteristics in various types of cancer that are approved for ICI use, especially for hematologic malignancies.

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Section: Discussionmentioning

confidence: 99%

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

et al. 2020

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“…In parallel, NTZ increased TCR expansion in PB (18). AHSCT, in turn, was found to result in a complete renewal of CD4+ T cells along with the persistence of selected CD8+ clones (11,12).…”

Section: Introductionmentioning

confidence: 85%

“…In MS patients, the TCR repertoire was investigated in blood, cerebrospinal fluid, and lesions (11,12). They found that CD4+ and CD8+ cells are expanded in CNS perivascular spaces and in MS lesions, respectively (13), and that Epstein-Barr virus (EBV)reactive clones are compartmentalized and expanded in MS brain (14).…”

Section: Introductionmentioning

confidence: 99%

The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies

et al. 2020

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has not yet been established hindering insight into the posttreatment TCR landscape of MS patients. To address this important knowledge gap, we tracked peripheral T-cell subpopulations (naive and memory CD4+ and CD8+) across 15 RRMS patients before and after 2 years of continuous treatment (NTZ) and a single treatment course (AHSCT) by high-throughput TCRβ sequencing. We found that the two MS treatments left treatment-specific multidimensional traces in patient TCRβ repertoire dynamics with respect to clonal expansion, clonal diversity, and repertoire architecture. Comparing MS TCR sequences with published datasets suggested that the majority of public TCRs belonged to virus-associated sequences. In summary, applying multidimensional computational immunology to a TCRβ dataset of treated MS patients, we show that qualitative changes of TCRβ repertoires encode treatment-specific information that may be relevant for future clinical trials monitoring and personalized MS follow-up, diagnosis, and treatment regimens.

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“…Based on these premises, the use of HSCs has been tested in numerous autoimmune diseases such as type 1 diabetes (T1D), multiple sclerosis (MS), systemic sclerosis, systemic lupus erythematosus and Chron's disease, with relevant benefits (3)(4)(5)(6). Indeed, HSCs may reset the immune response, thus reshaping the chronic derangement of the immune system to a more selftolerant state (7,8). Interestingly, it has been also demonstrated that the bone marrow-derived and blood HSCs are altered in some autoimmune conditions such as T1D and MS, with HSCs being scanty in the circulation and often unable to exploit their immunoregulatory function (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic Stem Cells in Type 1 Diabetes

Pastore

Assi²,

Nasr

et al. 2021

Front. Immunol.

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Despite the increasing knowledge of pathophysiological mechanisms underlying the onset of type 1 diabetes (T1D), the quest for therapeutic options capable of delaying/reverting the diseases is still ongoing. Among all strategies currently tested in T1D, the use of hematopoietic stem cell (HSC)-based approaches and of teplizumab, showed the most encouraging results. Few clinical trials have already demonstrated the beneficial effects of HSCs in T1D, while the durability of the effect is yet to be established. Investigators are also trying to understand whether the use of selected and better-characterized HSCs subsets may provide more benefits with less risks. Interestingly, ex vivo manipulated HSCs showed promising results in murine models and the recent introduction of the humanized mouse models accelerated the translational potentials of such studies and their final road to clinic. Indeed, immunomodulatory as well as trafficking abilities can be enhanced in genetically modulated HSCs and genetically engineered HSCs may be viewed as a novel “biologic” therapy, to be further tested and explored in T1D and in other autoimmune/immune-related disorders.

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Resetting the T Cell Compartment in Autoimmune Diseases With Autologous Hematopoietic Stem Cell Transplantation: An Update

Cited by 15 publications

References 38 publications

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies

Hematopoietic Stem Cells in Type 1 Diabetes

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