Rapid depletion of intratumoral regulatory T cells induces synchronized CD8 T- And NK-cell activation and IFNg-dependent tumor vessel regression

Yutaka Kurebayashi, Colleen P. Olkowski, Kelly C. Lane, Olga V. Vasalatiy, Biying C. Xu, Ryuhei Okada, Aki Furusawa, Peter L. Choyke, Hisataka Kobayashi, Noriko Sato

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Regulatory T cells (Tregs) are known to inhibit antitumor immunity, yet the specific mechanism by which intratumoral Tregs promote tumor growth remains unclear. To better understand the roles of intratumoral Tregs, we selectively depleted tumor-infiltrating Tregs using anti-CD25-F(ab0)2 near-infrared photoimmunotherapy. Depletion of tumor-infiltrating Tregs induced transient but synchronized IFNg expression in CD8 T and natural killer (NK) cells. Despite the small fraction of CD8 T and NK cells contained within examined tumors, IFNg produced by these CD8 T and NK cells led to efficient and rapid tumor vessel regression, intratumoral ischemia, and tumor necrosis/apoptosis and growth suppression. IFNg receptor expression on vascular endothelial cells was required for these effects. Similar findings were observed in the early phase of systemic Treg depletion in tumor-bearing Foxp3DTR mice; combination with IL15 therapy further inhibited tumor growth and achieved increased complete regression. These results indicate the pivotal roles of intratumoral Tregs in maintaining tumor vessels and tumor growth by suppressing CD8 T and NK cells from producing IFNg, providing insight into the mechanism of Treg-targeting therapies.

本文言語English
ページ(範囲)3092-3104
ページ数13
ジャーナルCancer Research
81
11
DOI
出版ステータスPublished - 2021 6月 1
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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