Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation

Hyungsin Kim, Jeongsoo Kim, Jason K. Sa, Byung Kyu Ryu, Kyung Jae Park, Jiyoung Kim, Hyojeong Ha, Yejin Park, Min Hwa Shin, Jungwon Kim, Hyemin Lee, Daham Kim, Kyunghye Lee, Byunghyun Jang, Kyung-Mi Lee, Shin-Hyuk Kang

Research output: Contribution to journalArticlepeer-review

Abstract

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically “cold” tumors into “hot” tumors. Data availability: Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request.

Original languageEnglish
Article number113553
JournalBiomedicine and Pharmacotherapy
Volume154
DOIs
Publication statusPublished - 2022 Oct

Keywords

  • Antitumor immunity
  • Calcipotriol
  • Glioblastoma
  • TSLP/CD4+T cell axis

ASJC Scopus subject areas

  • Pharmacology

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