Functional coexpression of Interleukin (IL)‐7 and its receptor (IL‐7R) on Hodgkin and Reed‐Sternberg cells: Involvement of IL‐7 in tumor cell growth and microenvironmental interactions of Hodgkin's lymphoma

International Journal of Cancer - Tập 125 Số 5 - Trang 1092-1101 - 2009
Lara Cattaruzza1, Annunziata Gloghini2, Karin Olivo1, Raffaele Di Francia3, Debora Lorenzon4, Rosaria De Filippi5,3, Antonino Carbone2, Alfonso Colombatti6,1,7, Antonio Pinto3, Donatella Aldinucci1
1Experimental Oncology 2, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN, Italy
2Department of Pathology, IRCCS-National Cancer Institute, Milan, Italy
3Hematology-Oncology and Stem Cells Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale", Naples, Italy
4Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN, Italy
5Department of Cellular and Molecular Biology and Pathology, Faculty of Biotechnological Sciences, Federico II University, Naples, Italy
6Department of Biomedical Science and Technology, University of Udine, Udine, Italy
7dMATI (Microgravity Ageing Training Immobility) Excellence Center, University of Udine, Udine, Italy

Tóm tắt

AbstractThe clinical and pathological features of classical Hodgkin lymphoma (cHL) mirror an abnormal tissue and systemic immune response due to the production of a variety of cytokines and chemokines by the malignant Hodgkin‐Reed‐Sternberg (H‐RS) cells and/or surrounding reactive cells. Here, we demonstrate that HL‐derived cell lines (L‐428, KM‐H2, HDLM‐2, L‐1236 and L‐540) and primary H‐RS cells from lymph node tissues of HL patients express the IL‐7(R) receptor. IL‐7 appears to be involved in autocrine circuitries of HL because L‐1236, HDLM‐2 and KM‐H2 cells display the constitutive production of IL‐7 and neutralizing anti‐IL‐7 antibodies induces a statistically significant inhibition of their basal proliferation. In addition, IL‐7, either exogenous or fibroblasts‐derived, promotes the clonogenic growth and reduces apoptosis of cultured H‐RS cells, being also able to partially protect these cells from the cytotoxic effects of doxorubicin. We also provide evidence that IL‐7 stimulates IL‐6 secretion from IL‐7R‐expressing fibroblasts from HL‐involved lymph nodes (HLFs), and that a striking increase in IL‐6 secretion can be observed in cocultures of HLFs with L1236 cells. Finally, we show that L‐1236 cells‐derived IL‐7 represents a costimulator for proliferation of purified CD4+CD25+CD127dim/− regulatory T cells (Tregs). Taken together, our data indicates that the IL‐7/IL‐7R axis constitutes an additional signaling pathway between H‐RS cells and their reactive cellular background, thereby affecting proliferation and survival of tumor cells, acting as a cofactor for Tregs expansion and enhancing the microenviromental production of IL‐6, a cytokine associated with the presence of “B” symptoms and a poor outcome in HL patients. © 2009 UICC

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International Journal of Cancer

Tập 125 Số 5

1092-1101

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