TY  - JOUR
A1  - Haist, Maximilian
A1  - Stege, Henner
A1  - Lang, Berenice Mareen
A1  - Tsochataridou, Aikaterini
A1  - Salzmann, Martin
A1  - Mohr, Peter
A1  - Schadendorf, Dirk
A1  - Ugurel, Selma
A1  - Placke, Jan-Malte
A1  - Weichenthal, Michael
A1  - Gutzmer, Ralf
A1  - Leiter, Ulrike
A1  - Kaatz, Martin
A1  - Haferkamp, Sebastian
A1  - Berking, Carola
A1  - Heppt, Markus
A1  - Tschechne, Barbara
A1  - Schummer, Patrick
A1  - Gebhardt, Christoffer
A1  - Grabbe, Stephan
A1  - Loquai, Carmen
T1  - Response to first-line treatment with immune-checkpoint inhibitors in patients with advanced cutaneous squamous cell carcinoma: a multicenter, retrospective analysis from the German ADOReg registry
JF  - Cancers
N2  - Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical studies, but data from real-world cohorts and trial-ineligible cSCC patients are limited. We retrospectively investigated patients with advanced cSCC who have been treated with CPI in a first-line setting at eight German skin cancer centers registered within the multicenter registry ADOReg. Clinical outcome parameters including response, progression-free (PFS) and overall survival (OS), time-to-next-treatment (TTNT), and toxicity were analyzed and have been stratified by the individual immune status. Among 39 evaluable patients, the tumor response rate (rwTRR) was 48.6%, the median PFS was 29.0 months, and the median OS was not reached. In addition, 9 patients showed an impaired immune status due to immunosuppressive medication or hematological diseases. Our data demonstrated that CPI also evoked tumor responses among immunocompromised patients (rwTRR: 48.1 vs. 50.0%), although these responses less often resulted in durable remissions. In line with this, the median PFS (11 vs. 40 months, p = 0.059), TTNT (12 months vs. NR, p = 0.016), and OS (29 months vs. NR, p < 0.001) were significantly shorter for this patient cohort. CPI therapy was well tolerated in both subcohorts with 15% discontinuing therapy due to toxicity. Our real-world data show that first-line CPI therapy produced strong and durable responses among patients with advanced cSCC. Immunocompromised patients were less likely to achieve long-term benefit from anti-PD1 treatment, despite similar tumor response rates.
KW  - advanced cutaneous squamous cell carcinoma
KW  - checkpoint inhibitor therapy
KW  - cemiplimab
KW  - immunosuppression
KW  - response durability
KW  - real-world data
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297506
SN  - 2072-6694
VL  - 14
IS  - 22
ER  - 
TY  - JOUR
A1  - Chopra, Martin
A1  - Lang, Isabell
A1  - Salzmann, Steffen
A1  - Pachel, Christina
A1  - Kraus, Sabrina
A1  - Bäuerlein, Carina A.
A1  - Brede, Christian
A1  - Jordán Garrote, Ana-Laura
A1  - Mattenheimer, Katharina
A1  - Ritz, Miriam
A1  - Schwinn, Stefanie
A1  - Graf, Carolin
A1  - Schäfer, Viktoria
A1  - Frantz, Stefan
A1  - Einsele, Hermann
A1  - Wajant, Harald
A1  - Beilhack, Andreas
T1  - Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1
JF  - PLoS ONE
N2  - Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.
KW  - Bioluminescence
KW  - cancer treatment
KW  - cell staining
KW  - cytokines
KW  - immune cells
KW  - metastasis
KW  - regulatory T cells
KW  - T cells
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97246
ER  - 
TY  - JOUR
A1  - Bonig, Halvard
A1  - Kuçi, Zyrafete
A1  - Kuçi, Selim
A1  - Bakhtiar, Shahrzad
A1  - Basu, Oliver
A1  - Bug, Gesine
A1  - Dennis, Mike
A1  - Greil, Johann
A1  - Barta, Aniko
A1  - Kállay, Krisztián M.
A1  - Lang, Peter
A1  - Lucchini, Giovanna
A1  - Pol, Raj
A1  - Schulz, Ansgar
A1  - Sykora, Karl-Walter
A1  - Teichert von Luettichau, Irene
A1  - Herter-Sprie, Grit
A1  - Ashab Uddin, Mohammad
A1  - Jenkin, Phil
A1  - Alsultan, Abdulrahman
A1  - Buechner, Jochen
A1  - Stein, Jerry
A1  - Kelemen, Agnes
A1  - Jarisch, Andrea
A1  - Soerensen, Jan
A1  - Salzmann-Manrique, Emilia
A1  - Hutter, Martin
A1  - Schäfer, Richard
A1  - Seifried, Erhard
A1  - Paneesha, Shankara
A1  - Novitzky-Basso, Igor
A1  - Gefen, Aharon
A1  - Nevo, Neta
A1  - Beutel, Gernot
A1  - Schlegel, Paul-Gerhardt
A1  - Klingebiel, Thomas
A1  - Bader, Peter
T1  - Children and adults with Refractory acute Graft-versus-Host Disease respond to treatment with the Mesenchymal Stromal cell preparation “MSC-FFM”—Outcome report of 92 patients
JF  - Cells
N2  - (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
KW  - graft-versus host
KW  - transplantation
KW  - mesenchymal stromal cell
KW  - cell therapy
KW  - hospital exemption
KW  - steroid-resistant aGvHD
KW  - refractory aGvHD
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193878
SN  - 2073-4409
VL  - 8
IS  - 12
ER  -