High-dose cyclophosphamide-mediated anti-tumor effects by the superior expansion of CD44high cells after their selective depletion

So Hee Hong, Il Hee Yoon, Yong Hee Kim, Seung Ha Yang, Min Jung Park, Hye Young Nam, Bongi Kim, Youngji Kim, Chan Sik Park, Chung Gyu Park

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

As alkylating agents, cyclophosphamides (CTX) are used to treat various cancers and, ironically, to boost immune responses. In the present study, we attempted to elucidate the mechanism responsible for the immunomodulatory effect of high-dose CTX in an established tumor model. A single injection of high-dose CTX increased the survival rate of immunocompetent, but not immunodeficient, mice. Notably, 10 days after CTX injection, the number of CD44high memory T cells significantly increased, without a selective decrease in the actual number and percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs). However, the proportion of Tregs among CD4+ T cells decreased due to expansion of memory and other CD4+ T cell subtypes. This outcome was accompanied by an increase in IL-15 mRNA and up-regulation of IL-15 receptors in the CD44+CD8+ T cell compartment. We postulate that the CTX-induced change in T cell balance may increase anti-tumor immunity.

Original languageEnglish
Pages (from-to)182-193
Number of pages12
JournalImmunobiology
Volume215
Issue number3
DOIs
StatePublished - Mar 2010

Bibliographical note

Funding Information:
This study was supported by the grant of the Korea Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center (TIMRC) at Seoul National University College of Medicine(C-G Park).

Keywords

  • Anti-tumor effects
  • Cyclophosphamide
  • IL-15/IL-15R
  • Memory T cell
  • Regulatory T cell

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