2. Academic Validation
  3. Tumor-derived osteopontin suppresses antitumor immunity by promoting extramedullary myelopoiesis

Tumor-derived osteopontin suppresses antitumor immunity by promoting extramedullary myelopoiesis

  • Cancer Res. 2014 Nov 15;74(22):6705-16. doi: 10.1158/0008-5472.CAN-14-1482.
Eun-Kyung Kim 1,  Insu Jeon 2,  Hyungseok Seo 2,  Young-Jun Park 1,  Boyeong Song 2,  Kyoo-A Lee 1,  Yongwoo Jang 2,  Yeonseok Chung 1,  Chang-Yuil Kang 3
Affiliations

Affiliations

  • 1 Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea.
  • 2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea.
  • 3 Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea. cykang@snu.ac.kr.
PMID: 25273090 DOI: 10.1158/0008-5472.CAN-14-1482
Abstract

Extramedullary myelopoiesis occurs commonly in tumor-bearing Animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly understood. In this study, we found that Osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the ERK1/2-MAPK pathway. Osteopontin-mediated extramedullary myelopoiesis was directly associated with increased MDSCs in tumor-bearing hosts. More importantly, Osteopontin silencing in tumor cells delayed both tumor growth and extramedullary myelopoiesis, while the same treatment did not affect tumor growth in vitro. Finally, treatment with an antibody against Osteopontin inhibited tumor growth and synergized with cell-based immunotherapeutic vaccines in mediating antitumor immunity. Our findings unveil a novel immunosuppressive role for tumor-derived Osteopontin and offer a rationale for its therapeutic targeting in Cancer treatment.

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