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Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic haematopoietic stem cell transplantation (allo-HSCT). GvHD can occur in almost every tissue, with the skin, liver, and intestines being the mainly affected organs. T cells are implicated in initiating GvHD. T cells identify a broad range of antigens and mediate the immune response through receptors on their surfaces (T cell receptors, TCRs). The composition of TCRs within a T cell population defines the TCR repertoire of an individual, and this repertoire represents exposure to self and non-self proteins. Monitoring the changes in the TCR repertoire using TCR sequencing can provide an indication of the dynamics of a T cell population. Monitoring the frequency and specificities of specific TCR clonotypes longitudinally in different conditions and specimens (peripheral blood, GvHD-affected tissue samples) can provide insights into factors modulating immune reactions following allogeneic transplantation and will help to understand the underlying mechanisms mediating GvHD. This review provides insights into current studies of the TCR repertoire in GvHD and potential future clinical implications of TCR sequencing.

Graft-versus-host disease (GvHD) of the skin is a severe allo-immune reaction and complication following allogeneic stem cell transplantation. Over the past years, intensive pre-clinical research has led to an improved understanding of the pathophysiology of acute and to a lesser extend chronic GvHD. This has translated into the approval of several new agents for the treatment of both forms of GvHD. This review summarizes the most recent advances in underlying pathomechanisms, clinical trials and newly approved agents for GvHD, with a special focus on skin involvement.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach for patients with certain hematological diseases, including several forms of lymphoma and leukemia. Besides several treatment-associated risks, transplanted patients are at an increased risk of developing osteoporosis. The underlying pathophysiology is complex and includes factors influenced directly by the disease as well as applied therapies like irradiation, chemotherapy and adjuvant immunosuppressive agents. In addition, patients are prone to secondary hypogonadism, and many patients will require long-term glucocorticoid therapy to mitigate graft-versus-host reactions. All these factors contribute to bone loss, but the individual risk profile may vary greatly. This review summarizes our knowledge on bone loss following allogenic HCT and provides screening and treatment recommendations.

Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T-cell receptor repertoire remains largely unknown. Using next-generation sequencing, the T-cell receptor alpha (TRα) repertoire of naive and memory CD8+ T cells from 25 patients who had received different forms of allogeneic transplantation was analyzed. In parallel, reconstitution of the CD8+/CD4+ T-cell subsets was mapped using flow cytometry. When comparing the influence of anti-T-cell therapy, a delay in the reconstitution of the naive CD8+ T-cell repertoire was observed in patients who received in vivo T-cell depletion using antithymocyte globulin or post-transplantation cyclophosphamide in case of haploidentical transplantation. Sequencing of the TRα identified a repertoire consisting of more dominant clonotypes (>1% of reads) in these patients at 6 and 18 months post transplantation. When comparing donor and recipient, approximately 50% and approximately 80% of the donors’ memory repertoire were later retrieved in the naive and memory CD8+ T-cell receptor repertoire of the recipients, respectively. Although there was a remarkable expansion of single clones observed in the recipients’ memory CD8+ TRα repertoire, no clear association between graft-versus-host disease or cytomegalovirus infection and T-cell receptor diversity was identified. A lower TRα diversity was observed in recipients of a cytomegalovirus-seropositive donor (P=0.014). These findings suggest that CD8+ T-cell reconstitution in transplanted patients is influenced by the use of T-cell depletion or immunosuppression and the donor repertoire.

Background: Semaphorin 4D (Sema4D) is a glycoprotein that inhibits bone formation and has been associated with cancer progression and the occurrence of bone metastases. Recently, Sema4D expression has been linked to estrogen signaling in breast cancer. Endocrine therapies like tamoxifen and aromatase inhibitors (AI) are a standard therapeutic approach in hormone receptor positive breast cancers. Tamoxifen exerts ER-agonistic effects on bone, whereas AI negatively affect bone health by increasing resorption and fracture risk. The effect of endocrine therapies on circulating Sema4D levels in breast cancer patients has not been investigated yet. Methods: We measured circulating Sema4D plasma levels at primary diagnosis and in a follow-up sample 12 months after surgery in a cohort of 46 pre- and postmenopausal women with primary estrogen receptor positive breast cancer receiving adjuvant tamoxifen or AI. Results: The mean baseline levels ± SD for Sema4D were 441.6 ± 143.4 pmol/l. No significant differences in total plasma Sema4D were observed when stratifying the patients according to age, menopausal status, tumor subtype, nodal and hormone receptor status, or tumor size. However, Sema4D levels were significantly reduced by 28% (p