Radiation-induced fibrotic tumor microenvironment regulates anti-tumor immune response

Jae Kyung Nam, Ji Hee Kim, Min Sik Park, Eun Ho Kim, Joon Kim, Yoon Jin Lee

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


High linear energy transfer (LET) radiation, such as neutron radiation, is considered more effective for the treatment of cancer than low LET radiation, such as X-rays. We previously reported that X-ray irradiation induced endothelial-to-mesenchymal transition (EndMT) and profibrotic changes, which contributed to the radioresistance of tumors. However, this effect was attenuated in tumors of endothelial-specific Trp53-knockout mice. Herein, we report that compared to X-ray irradi-ation, neutron radiation therapy reduced collagen deposition and suppressed EndMT in tumors. In addition to the fewer fibrotic changes, more cluster of differentiation (CD8)-positive cytotoxic T cells were observed in neutron-irradiated regrowing tumors than in X-ray-irradiated tumors. Furthermore, lower programmed death-ligand 1 (PD-L1) expression was noted in the former. Endothelial-specific Trp53 deletion suppressed fibrotic changes within the tumor environment following both X-ray and neutron radiation therapy. In particular, the upregulation in PD-L1 expression after X-ray radiation therapy was significantly dampened. Our findings suggest that compared to low LET radiation therapy, high LET radiation therapy can efficiently suppress profibrotic changes and enhance the anti-tumor immune response, resulting in delayed tumor regrowth.

Original languageEnglish
Article number5232
Issue number20
Publication statusPublished - 2021 Oct 1

Bibliographical note

Funding Information:
Funding: This work was supported by grants from the National Research Foundation (NRF-2020M2D9A2093964 and NRF-2020R1A2B5B02002709) and a grant from the Korea Institute of Radiologic and Medical Sciences (KIRAMS, 50531–2021), funded by the Ministry of Science and ICT (MSIT), Korea.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Anti-tumor immune response
  • Fibrotic tumor microenvironment
  • High linear energy transfer
  • Neutron radiation therapy
  • Programmed death-ligand 1
  • X-ray radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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