Blocking IL1β pathway following paclitaxel chemotherapy slightly inhibits primary tumor growth but promotes spontaneous metastasis

Tali Voloshin, Dror Alishekevitz, Limor Kaneti, Valeria Miller, Elina Isakov, Irena Kaplanov, Elena Voronov, Ella Fremder, Moran Benhar, Marcelle Machluf, Ron N. Apte, Yuval Shaked

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Acquired resistance to therapy is a major obstacle in clinical oncology, and little is known about the contributing mechanisms of the host response to therapy. Here, we show that the proinflammatory cytokine IL1β is overexpressed in response to paclitaxel chemotherapy in macrophages, subsequently promoting the invasive properties of malignant cells. In accordance, blocking IL1β, or its receptor, using either genetic or pharmacologic approach, results in slight retardation of primary tumor growth; however, it accelerates metastasis spread. Tumors from mice treated with combined therapy of paclitaxel and the IL1 receptor antagonist anakinra exhibit increased number of M2 macrophages and vessel leakiness when compared with paclitaxel monotherapy-treated mice, indicating a prometastatic role of M2 macrophages in the IL1β-deprived microenvironment. Taken together, these findings demonstrate the dual effects of blocking the IL1 pathway on tumor growth. Accordingly, treatments using "add-on" drugs to conventional therapy should be investigated in appropriate tumor models consisting of primary tumors and their metastases.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalMolecular Cancer Therapeutics
Volume14
Issue number6
DOIs
StatePublished - 1 Jun 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Blocking IL1β pathway following paclitaxel chemotherapy slightly inhibits primary tumor growth but promotes spontaneous metastasis'. Together they form a unique fingerprint.

Cite this