[Impact of LAight therapy on hidradenitis suppurativa care]. / Einfluss der LAight-Therapie auf die Versorgung der Acne inversa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease with high burden for patients and limited treatment options. We recently analyzed the efficacy of local treatment with LAight therapy, a combination of intense pulsed light (IPL) and radiofrequency (RF). OBJECTIVES: The aim of the present survey was to compare care of HS patients under LAight with standard care prior to therapy. MATERIALS AND METHODS: The retrospective study included 111 patients who were treated with LAight at least 5 times between 01/2014 and 03/2017. Primary endpoint was the change in surgical interventions. Secondary endpoints included additional patient-reported outcomes, e.g., effects on their quality of life. RESULTS: In all, 50 completed surveys were available for evaluation. Under LAight therapy, the number of surgical interventions decreased from 3.2 to 0.3 per year (p < 0.001). Secondary endpoints were also significantly improved: The days of sick leave/year due to HS decreased from 30.4 to 7.2 (p = 0.002), and the number of doctor appointments due to HS flare ups was altered from 7.3 to 1.5 (p < 0.001). In line, patient-reported pain levels, general wellbeing and quality of life were also improved. CONCLUSION: This retrospective assessment of patient-reported treatment outcomes of 50 HS cases after treatment with LAight revealed a significant reduction of required surgical interventions and sick-days along with improved quality of life. Thus, it appears that IPL + RF treatment not only improves disease activity, but also secondary care aspects. Future studies will need to confirm these findings in a controlled setting.

Immune signature as predictive marker for response to checkpoint inhibitor immunotherapy and overall survival in melanoma.

BACKGROUND: Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. METHODS: This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count. RESULTS: Responders to ICI therapy displayed an abundance of proliferating CD4+ T cells, an increased lymphocyte-to-monocyte ratio, a low platelet-to-lymphocyte ratio, low levels of CTLA-4+ Treg, and (arginase 1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). Nevertheless, non-responders with similar immune cell compositions also benefited from therapy displaying increased long-term OS. CONCLUSIONS: Our study demonstrated that the observed immune signature in the peripheral blood of melanoma patients prior to treatment could identify responders as well as non-responders that benefit from ICI immunotherapies.

Platelet-Derived GARP Induces Peripheral Regulatory T Cells-Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis.

Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet-T cell interaction in immune-mediated diseases remains limited. Glycoprotein A repetitions predominant (GARP) expressed on platelets and on activated regulatory T cells (Treg) is involved in the regulation of peripheral immune responses by modulating the bioavailability of transforming growth factor ß (TGF-ß). Soluble GARP (sGARP) exhibits strong regulatory and anti-inflammatory capacities both in vitro and in vivo, leading to the induction of peripheral Treg. Herein, we investigated the effect of platelet-derived GARP on the differentiation, phenotype, and function of T effector cells. CD4+CD25- T cells cocultured with platelets upregulated FoxP3, the master transcription factor for Treg, were anergic, and were strongly suppressive. These effects were reversed by using a blocking anti-GARP antibody, indicating a dependency on GARP. Importantly, melanoma patients in different stages of disease showed a significant upregulation of GARP on the platelet surface, correlating to a reduced responsiveness to immunotherapy. In conclusion, our data indicate that platelets induce peripheral Treg via GARP. These findings might contribute to diseases such as cancer-associated thrombocytosis, wherein poor prognosis and metastasis are associated with high counts of circulating platelets.