Characterization of tumor-infiltrating B-cells in cutaneous T-cell lymphoma
Final Report Abstract
Primary cutaneous T cell lymphomas (CTCL) represent a rare and heterogeneous group of hematologic malignancies that occur mainly in older people and originate from skin resident T lymphocytes. The most common form of CTCL are Mycosis Fungoides and Sezary Syndrome. The prognosis is generally good in early stages (EORTC stage IA-IIA), but life expectancy drops dramatically in tumor and advanced stages (IIB-IVB). In addition to the advanced tumor stage, other biological factors also play a role in the higher aggressiveness. These include a large cell transformation, an age of over 60 years and an elevated LDH level in the blood. Nevertheless, the biology of aggressive CTCL is ultimately not fully understood, which is also due to the cellular and genetic heterogeneity and rarity of the disease. In our preliminary work, we were able to show that increased infiltration by B lymphocytes (B cells) in CTCL tumor tissue is associated with a poorer prognosis and occurs primarily at higher tumor stages. Anecdotally, we observed that a specific depletion of B cells by the therapeutic antibody rituximab was able to induce remission of a large CTCL skin tumor and regional lymph nodes. Within the tumor microenvironment B cell depletion was followed by local re-shaped reactive T cell infiltration leading to an enhanced anti-tumor immune response. The aim of this research project was therefore to identify underlying mechanisms by which infiltrating B cells could mediate the biology of CTCL. Our data suggest that B cells are attracted and activated by CTCL cells in cell culture models. In addition, in the presence of activated B cells, CTCL cells exhibited significantly higher proliferation accompanied by metabolic reprogramming leading to higher energy production. In the tumor tissue of patients with aggressive and B-cell-rich CTCL, spatial analysis revealed that B cells were surrounded by macrophages with a so-called M2 polarization. M2 macrophages have already been described as a tumor-driving immune cell population in various types of cancer and also in CTCL due to their immunosuppressive properties. Loco-regional differences in the cellular composition of CTCL tumor tissue were also found, which could also be traced on the level of specific gene expression profiles in B-cell-rich versus B-cell-poor tumor areas. Overall, our results suggest that B cells might influence the biology of CTCL indirectly via the accumulation of M2 macrophages in the tumor microenvironment. Ongoing research aims to address the specific molecular mechanisms of this interplay ultimately trying to identify novel therapeutic targets.
Publications
-
Treatment‐specific evaluation of the modified Glasgow‐Prognostic‐Score in patients with advanced cutaneous melanoma. Journal of the European Academy of Dermatology and Venereology, 35(12).
Pflug, N.; Vitus, M.; Knuever, J.; Hamacher, S.; Mauch, C.; Schlaak, M. & Theurich, S.
-
3. Interdisziplinäres Symposium „Kutane Lymphome in Klinik und Praxis“. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 20(9), 1281-1282.
Klemke, Claus‐Detlev & Theurich, Sebastian
-
Characterization of Tumorinfiltrating B Cells in Patients with cutaneous T-Cell Lymphoma. Oncology Research and Treatment (2022), Volume: 45 Suppl 2, Issue: SUPPL 2, p.255-255, Print-ISSN: 2296-5270
Oganesian, S.; Piontek, G.; Heide, M.; Dalli, I.; Kirmaier, M.; Hadzic, A.; Posch, C.; Weigert, O.; Rudelius, M.; von Bergwelt-Baildon, M. & Theurich, S.
-
Clofarabine followed by reduced intensity conditioning as a sequential concept prior to allogeneic HSCT in three patients with advanced staged cutaneous t cell lymphoma. In BONE MARROW TRANSPLANTATION (Vol. 57, No. SUPPL 1, pp. 177-177).
Stauffer, E., Fraccaroli, A., Drolle, H., Flaig, M., Heinzerling, L., von Bergwelt, M., Theurich, S. & Tischer, J.
-
Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer. American Journal of Physiology-Cell Physiology, 323(3), C879-C884.
Schenk, Alexander; Esser, Tobias; Belen, Sergen; Gunasekara, Nadira; Joisten, Niklas; Winker, Matteo Thomas; Weike, Lea; Bloch, Wilhelm; Heidenreich, Axel; Herden, Jan; Löser, Heike; Oganesian, Sabine; Theurich, Sebastian; Watzl, Carsten & Zimmer, Philipp
-
Indolente kutane T-Zell-Lymphome. Indolente Lymphome, 231-254. Springer International Publishing.
Willemze, Rein; Theurich, Sebastian & Schlaak, Max
-
P06.02 Spatio-functional characterization of tumor-infiltrating B cells in the tumor microenvironment of cutaneous T cell lymphoma. Poster Presentations, A23.2-A24. BMJ Publishing Group Ltd.
Oganesian, S.; Funk, M.; Hadzic, A.; Kirmaier, M.; Piontek, G.; Watter, J.; Heide, M.; Krebs, S.; Mages, S.; Blum, H.; Posch, C.; Weigert, O.; Klughammer, J.; Rudelius, M.; Bergwelt-Baildon, M. & Theurich, S.
