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Sunitinib Treatment-elicited Distinct Tumor Microenvironment Dramatically Compensated the Reduction of

Sheng-Yung Fu1,2, Chun-Chieh Wang2,3,4, Fang-Hsin Chen2,3,4

  • 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

In Vivo (Athens, Greece)
|May 2, 2020
PubMed
Abstract

Insights

Tyrosine kinase inhibitor (TKI) monotherapy for prostate cancer shows limited efficacy. This study reveals that Sunitinib alters the tumor microenvironment, impairing TKI effectiveness by increasing myeloid-derived suppressor cells.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Prostate cancer exhibits a low clinical response rate to tyrosine kinase inhibitor (TKI) monotherapy.
  • Mechanisms underlying TKI resistance in prostate cancer remain largely undefined.
  • The role of the tumor microenvironment (TME) in TKI resistance is an area requiring further investigation.

Purpose of the Study:

  • To investigate the involvement of the tumor microenvironment (TME) in resistance to tyrosine kinase inhibitors (TKIs).
  • To elucidate the effects of Sunitinib (Sutent) on the TME in prostate cancer models.

Main Methods:

  • Examined the anti-vascular effects of Sutent using immunofluorescent staining in TRAMP-C1 tumors.
  • Quantified CD11b+ cell populations via flow cytometry.
  • Measured cytokine and chemokine levels using multiplex immunoassay.

Main Results:

  • Sunitinib monotherapy resulted in a 1.5-day tumor growth delay, induced chronic hypoxia, and promoted vasculature maturation.
  • Sunitinib treatment increased the proportion of polymorphonuclear myeloid-derived suppressor cells (MDSCs) in peripheral blood.
  • The altered TME led to myeloid cell redistribution in hypoxic regions, with elevated cytokine and chemokine levels observed in both tumors and blood.

Conclusions:

  • Sunitinib treatment establishes a unique tumor microenvironment.
  • This induced TME hinders the effective reduction of myeloid-derived suppressor cells (MDSCs) by TKIs.
  • The findings suggest TME modulation as a critical factor in TKI resistance in prostate cancer.
Keywords:
Tyrosine kinase inhibitorangiogenesishypoxiamyeloid-derived suppressor cellsperipheral bloodsunitinibtumor-associated macrophage

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