Potentials of interleukin-27 (IL-27) as an immunotherapeutic cytokine in cancer therapy

Wei Boon Yap, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen


Cancer immunotherapy using cytokines has been sought as an alternative therapeutic approach for treating cancers. Besides remarkable immunoregulatory properties, interleukin (IL)-27 has recently been shown to possess promising anticancer functions; hence, its potential roles in cancer immunotherapy. Although proven to be effective against cancer cell growth and angiogenesis, given its dual immune-regulating functions (pro-inflammatory and anti-inflammatory), the use of IL-27 as a cancer immunotherapeutic cytokine could possibly be a two-edged sword without meticulous and thorough research. This mini-review mainly discusses the functions and future prospects of IL-27 as an effective anticancer cytokine. Hopefully, it imparts useful insights into the potential applications of IL-27 in cancer immunotherapy


interleukins; IL-27; cytokines; immunotherapy; cancers

Full Text:



Bekaii-Saab TS, Roda JM, Guenterberg KD, et al. A phase I trial of paclitaxel and trastuzumab in combination with interleukin-12 in patients with HER2/neu-expressing malignancies. Mol Cancer Ther 2009; 8(11): 2983–2991. doi: 10.1158/1535-7163.MCT-09-0820.

Tugues S, Burkhard SH, Ohs I, et al. New insights into IL-12-mediated tumor suppression. Cell Death Differ 2015; 22: 237–246. doi: 10.1038/cdd.2014.134.

Zhang JM, An JX. Cytokines, inflammation and pain. Int Anesthesiol Clin 2007; 45(2): 27–37. doi: 10.1097/AIA.0b013e318034194e.

Sorensen EW, Gerber SA, Frelinger JG, et al. IL-12 suppresses vascular endothelial growth factor receptor 3 expression on tumor vessels by two distinct IFN-γ-dependent mechanisms. J Immunol 2010; 184(4): 1858–1866. doi: 10.4049/jimmunol.0903210.

Lee S, Margolin K. Cytokines in cancer immunotherapy. Cancers 2011; 3: 3856–3893. doi: 10.3390/cancers3043856.

Shi X, Liu J, Xiang Z, et al. Gene expression analysis in interleukin-12-induced suppression of mouse mammary carcinoma. Int J Cancer 2004; 110(4): 570–578. doi: 10.1002/ijc.20145.

Gollob JA, Mier J, Veenstra K, et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: Ability to maintain IFN-γ induction is associated with clinical response. Clinic Cancer Res 2000; 6: 1678–1692.

Yoshimoto T, Chiba Y, Furusawa JI, et al. Potential clinical application of interleukin-27 as an antitumor agent. Cancer Sci 2015; 106(9): 1103–1110. doi: 10.1111/cas.12731.

Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity 2002; 16(6):779–790.

Li MS, Liu ZZ, Liu JQ, et al. The Yin and Yang aspects of IL-27 in induction of cancer-specific T cell responses and immunotherapy. Immunotherapy 2015; 7(2): 191–200. doi: 10.2217/imt.14.95.

Hisada M, Kamiya S, Fujita K, et al. Potent antitumor activity of interleukin-27. Cancer Res 2004; 64: 1152–1156. doi: 10.1158/0008-5472.CAN-03-2084.

Canale S, Cocco C, Frasson C, et al. Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia 2011; 25(12): 1815–1824. doi: 10.1038/leu.2011.158.

Shimizu M, Shimamura M, Owaki T, et al. Antiangiogenic and antitumor activities of IL-27. J Immunol 2006; 176(12): 7317–7324. doi: 10.4049/jimmunol.176.12.7317.

Ho MY, Leu SJ, Sun GH, et al. IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediated activities. J Immunol 2009; 183(10): 6217–6226. doi: 10.4049/jimmunol.0901272.

Airoldi I, Tupone MG, Esposito S, et al. Interleukin-27 re-educates intratumoral myeloid cells and down-regulates stemness genes in non-small cell lung cancer. Oncotarget 2015; 6(6): 3694–3708. doi: 10.18632/oncotarget.2797.

Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010; 44(5): 479–496. doi: 10.3109/10715761003667554.

Ruiz-Ruiz C, Munõz-Pinedo C, López-Rivas A. Interferon-γ treatment elevates caspase-8 expression and sensitizes human breast tumor cells to a death receptor-induced mitochondria-operated apoptotic program. Cancer Res 2000; 60(20): 5673–5680.

DOI: http://dx.doi.org/10.24294/ti.v1.i3.121


  • There are currently no refbacks.

Copyright (c) 2017 Wei Boon Yap, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License

This site is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.