The IL-33/ST2 pathway suppresses murine colon cancer growth and metastasis by upregulating CD40 L signaling
| Autor: | Jingjing Li, Qing Deng, Shaorong Deng, Yan Yu, Xiaolan Yu, Hao Ye, Wei Han, Liya Jiang, Ping Luo, Yinjie Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes medicine.medical_treatment T-Lymphocytes CD40 Ligand Cancer immunotherapy RM1-950 Metastasis 03 medical and health sciences Mice 0302 clinical medicine Immune system Downregulation and upregulation Cell Movement medicine Animals Cell Proliferation Pharmacology CD40 biology Chemistry Interleukin General Medicine medicine.disease Interleukin-33 ST2 Interleukin-1 Receptor-Like 1 Protein Colorectal cancer Up-Regulation Interleukin 33 030104 developmental biology 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research biology.protein IL-33 Therapeutics. Pharmacology CD8 Signal Transduction CD40L signaling |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110232-(2020) |
| ISSN: | 0753-3322 |
| Popis: | Interleukin (IL)-33 is a member of the IL-1 family, participating in both helper T1 (Th1)- and Th2-type immune responses, but its ambiguous effects on tumor growth and related immune mechanisms remain unclear. Here, we report that recombinant mouse IL-33 (mIL-33) significantly inhibited colon cancer growth and metastasis to lung and liver in a murine CT26 or MC38 tumor-cell engraftment model. This effect could be associated with CD4+ T cells and CD40 L signaling, as depletion of CD4+ T cells or blocking CD40 L signaling in vivo partly abolished the antitumor function of IL-33. In addition, IL-33 treatment upregulated CD40 L expression on tumor-infiltrating lymphocytes, and promoted the activation of CD4+ T, CD8+ T and natural killer cells via CD40 L signaling. Furthermore, IL-33 was sufficient to induce the ST2 expression on CD4+ T cells, but not on CD8+ T and natural killer cells, indicating that IL-33 acted on CD4+ T cells via a positive-feedback loop. Our findings shed new light on the IL-33-mediated antitumor effects and mechanisms of Th1 action, and also suggest that IL-33 may serve as an activator to boost anticancer immune responses in singular or combinatory therapies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect