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Inhibition of IL‐6 signaling significantly reduces primary tumor growth and recurrencies in orthotopic xenograft models of pancreatic cancer
Author(s) -
Goumas Freya A.,
Holmer Reinhild,
Egberts JanHendrik,
Gontarewicz Artur,
Heneweer Carola,
Geisen Ulf,
Hauser Charlotte,
Mende MariaMargarete,
Legler Karen,
Röcken Christoph,
Becker Thomas,
Waetzig Georg H.,
RoseJohn Stefan,
Kalthoff Holger
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29445
Subject(s) - tocilizumab , medicine , gemcitabine , pancreatic cancer , cancer research , adjuvant , cytokine , cancer , oncology , disease
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human tumors, with radical surgical resection as the only curative treatment option. However, resection is only possible in a small fraction of patients, and about 80% of the patients develop recurrencies. PDAC development is facilitated by the cytokine interleukin‐6 (IL‐6), which acts via classic and trans‐signaling. Both pathways are inhibited by the anti‐IL‐6‐receptor antibody tocilizumab, whereas the fusion protein sgp130Fc specifically blocks trans‐signaling. Here, we show that conservative or adjuvant therapy with both inhibitors reduces tumor growth in an orthotopic model of human Colo357 cells in SCID/bg mice. In the conservative setting, median primary tumor weight was reduced 2.4‐fold for tocilizumab and 4.4‐fold for sgp130Fc. sgp130Fc additionally led to a decrease in microvessel density, which was not observed with tocilizumab. In the adjuvant therapeutic setting after surgical resection of the primary tumor, treatment with tocilizumab or sgp130Fc decreased the local recurrence rate from 87.5% in the control group to 62.5 or 50%, respectively. Furthermore, the median weight of the local recurrent tumors was clearly diminished, and both inhibitors reduced the number of distant metastases. A significant reduction of tumor weight and metastases—comparable to gemcitabine treatment—was also observed with both inhibitors in another model using the poorly differentiated PancTuI cells. Our findings demonstrate the inhibition of IL‐6 as a new treatment option in PDAC.