2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages

Wen Hua DUAN, Li Ya JIN, Zu Chao CAI, David LIM, Zhi Hui FENG

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors. Methods: Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses. Results: The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ. Conclusion: The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors via M1-polarized TAMs, and HPTA may be considered as a new therapeutic for amplifying the efficacy of local RT for non-targeted breast tumors.

Original languageEnglish
Pages (from-to)693-704
Number of pages12
JournalBiomedical and Environmental Sciences
Volume34
Issue number9
DOIs
Publication statusPublished - Sep 2021
Externally publishedYes

Keywords

  • 2-hexyl-4-pentylenic acid (HPTA)
  • Abscopal effect
  • Angiogenesis
  • Breast cancer
  • Polarization
  • Radiotherapy (RT)
  • Tumor-associated macrophages (TAMs)

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