Immunomodulatory and direct activities of ropeginterferon alfa‐2b on cancer cells in mouse models of leukemia. Issue 7 (2nd May 2022)

• Record Type: Journal Article
• Authors: Sakatoku, Kazuki; Nakashima, Yasuhiro; Nagasaki, Joji; Nishimoto, Mitsutaka; Hirose, Asao; Nakamae, Mika; Koh, Hideo; Hino, Masayuki; Nakamae, Hirohisa
• Is Part Of: Cancer science. Volume 113:Issue 7(2022)
• Page Start: 2246
• Page End: 2257
• Publication Date: 2022-05-02
• Subjects: adoptive immunity -- antitumor effector cells -- immunomodulatory effect -- interferon‐alpha -- ropeginterferon alfa‐2b; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15376
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Although ropeginterferon alfa‐2b has recently been clinically applied to hematological malignancies, the antitumor mechanism of ropeginterferon alfa‐2b has not been fully examined. The results of experiments in mouse models of leukemia suggest that the antitumor effect of ropeginterferon alfa‐2b is mainly mediated by immunomodulation. Furthermore, T‐cells may play a crucial role in this function.