Immunomodulatory and direct activities of ropeginterferon alfa-2b on cancer cells in mouse models of leukemia

Kazuki Sakatoku, Yasuhiro Nakashima, Joji Nagasaki, Mitsutaka Nishimoto, Asao Hirose, Mika Nakamae, Hideo Koh, Masayuki Hino, Hirohisa Nakamae

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Although ropeginterferon alfa-2b has recently been clinically applied to myeloproliferative neoplasms with promising results, its antitumor mechanism has not been thoroughly investigated. Using a leukemia model developed in immunocompetent mice, we evaluated the direct cytotoxic effects and indirect effects induced by ropeginterferon alfa-2b in tumor cells. Ropeginterferon alfa-2b therapy significantly prolonged the survival of mice bearing leukemia cells and led to long-term remission in some mice. Alternatively, conventional interferon-alpha treatment slightly extended the survival and all mice died. When ropeginterferon alfa-2b was administered to interferon-alpha receptor 1–knockout mice after the development of leukemia to verify the direct effect on the tumor, the survival of these mice was slightly prolonged; nevertheless, all of them died. In vivo CD4+ or CD8+ T-cell depletion resulted in a significant loss of therapeutic efficacy in mice. These results indicate that the host adoptive immunostimulatory effect of ropeginterferon alfa-2b is the dominant mechanism through which tumor cells are suppressed. Moreover, mice in long-term remission did not develop leukemia, even after tumor rechallenge. Rejection of rechallenge tumors was canceled only when both CD4+ and CD8+ T cells were removed in vivo, which indicates that each T-cell group functions independently in immunological memory. We show that ropeginterferon alfa-2b induces excellent antitumor immunomodulation in hosts. Our finding serves in devising therapeutic strategies with ropeginterferon alfa-2b.

Original languageEnglish
Pages (from-to)2246-2257
Number of pages12
JournalCancer Science
Volume113
Issue number7
DOIs
Publication statusPublished - Jul 2022
Externally publishedYes

Keywords

  • adoptive immunity
  • antitumor effector cells
  • immunomodulatory effect
  • interferon-alpha
  • ropeginterferon alfa-2b

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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