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Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity.
Yang, Shiang-Jie; Chang, Sheng-Tsung; Chang, Kung-Chao; Lin, Bo-Wen; Chang, Kwang-Yu; Liu, Yao-Wen; Lai, Ming-Derg; Hung, Liang-Yi.
Afiliación
  • Yang SJ; The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
  • Chang ST; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
  • Chang KC; Department of Pathology, Chi-Mei Medical Center, Tainan, 71004, Taiwan, ROC.
  • Lin BW; Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
  • Chang KY; Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
  • Liu YW; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
  • Lai MD; National Institute of Cancer Research, National Health Research Institutes, Tainan, 70456, Taiwan, ROC.
  • Hung LY; Department of Pathology, Kuo General Hospital, Tainan, 70054, Taiwan, ROC.
Cell Death Dis ; 15(1): 103, 2024 01 30.
Article en En | MEDLINE | ID: mdl-38291041
ABSTRACT
Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers. However, targeting Aurora-A has not yet got a breakthrough in clinical trials. Recent reports have indicated that inhibition of oncoproteins may reduce antitumor immunity, but the role of tumor-intrinsic Aurora-A in regulating antitumor immunity remains unclear. In this study, we demonstrated that in tumors with high lymphocyte infiltration (hot tumors), higher tumor-intrinsic Aurora-A expression is associated with a better prognosis in CRC patients. Mechanically, tumor-intrinsic Aurora-A promotes the cytotoxic activity of CD8+ T cells in immune hot CRC via negatively regulating interleukin-16 (IL-16), and the upregulation of IL-16 may impair the therapeutic effect of Aurora-A inhibition. Consequently, combination treatment with IL-16 neutralization improves the therapeutic response to Aurora-A inhibitors in immune hot CRC tumors. Our study provides evidence that tumor-intrinsic Aurora-A contributes to anti-tumor immunity depending on the status of lymphocyte infiltration, highlighting the importance of considering this aspect in cancer therapy targeting Aurora-A. Importantly, our results suggest that combining Aurora-A inhibitors with IL-16-neutralizing antibodies may represent a novel and effective approach for cancer therapy, particularly in tumors with high levels of lymphocyte infiltration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido