IL-33 Induces Sema4A Expression in Dendritic Cells and Exerts Antitumor Immunity
Autor: | Yu Futami, Akio Osa, Hyota Takamatsu, Kotaro Miyake, Yuki Hosono, Shingo Satoh, Izumi Nagatomo, Yuhei Kinehara, Satoshi Nojima, Yasuhiko Suga, Kiyoharu Fukushima, Atsushi Kumanogoh, Taro Koba, Haruhiko Hirata, Yujiro Naito, Yoshito Takeda, Shohei Koyama, Takeshi Nakatani, Takeshi Tsuda, Daisuke Okuzaki, Kota Iwahori, Daisuke Ito, Yoshimitsu Nakanishi, Masayuki Nishide, Takayuki Shiroyama |
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Rok vydání: | 2021 |
Předmět: |
Male
medicine.medical_treatment Immunology Semaphorins Biology Carcinoma Lewis Lung Mice Immune system Downregulation and upregulation Cancer immunotherapy medicine Immunology and Allergy Animals Humans Mice Knockout Immunity Cellular Cell Differentiation Dendritic cell Immunotherapy Dendritic Cells Interleukin-33 Interleukin 33 Gene Expression Regulation Neoplastic Mice Inbred C57BL Disease Models Animal Cytokine Cancer research CD8 Biomarkers Neoplasm Transplantation |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 207(5) |
ISSN: | 1550-6606 |
Popis: | Cancer immunotherapy has shown great promise as a new standard therapeutic strategy against cancer. However, the response rate and survival benefit remain unsatisfactory because most current approaches, such as the use of immune checkpoint inhibitors, depend on spontaneous antitumor immune responses. One possibility for improving the efficacy of immunotherapy is to promote antitumor immunity using adjuvants or specific cytokines actively. IL-33 has been a candidate for such cytokine therapies, but it remains unclear how and in which situations IL-33 exerts antitumor immune effects. In this study, we demonstrate the potent antitumor effects of IL-33 using syngeneic mouse models, which included marked inhibition of tumor growth and upregulation of IFN-γ production by tumor-infiltrating CD8+ T cells. Of note, IL-33 induced dendritic cells to express semaphorin 4A (Sema4A), and the absence of Sema4A abolished the antitumor activity of IL-33, indicating that Sema4A is intrinsically required for the antitumor effects of IL-33 in mice. Collectively, these results not only present IL-33 and Sema4A as potential therapeutic targets but also shed light on the potential use of Sema4A as a biomarker for dendritic cell activation status, which has great value in various fields of cancer research, including vaccine development. |
Databáze: | OpenAIRE |
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