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IL-34, IL-36 and IL-38 in colorectal cancer—key immunoregulators of carcinogenesis

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Abstract

Colorectal cancer (CRC) is still a big killer nowadays, but the precise underlying mechanism remains to be explored. It is believed that imbalance of host immunity in the local microenvironment plays a critical role in the tumorigenesis of CRC. IL-34 is inversely correlated with overall survival in CRC patients, perhaps via regulating terminal differentiation of a subset of macrophages (M2). It is believed that the recruitment/differentiation of M2 macrophages within the cancer simply represents an increase in number, but the function of these M2 macrophages may be compromised. IL-36s (IL-36α, β and γ) are constitutively expressed in non-cancer colon tissue, but colonic IL-36α, IL-36β and IL-36γ are substantially reduced in the CRC tissues (~ 80%). IL-36α is an independent factor affecting the survival of CRC patients. The level of IL-36α and/or IL-36γ in CRC tissue could potentially be used as biomarkers for predicting the prognosis of CRC at both the later or early stages of CRC. IL-38 is also an anti-inflammatory cytokine. Colonic IL-38 is ~ 95% lower in CRC compared to non-CRC colonic tissue, consistent with the positive correlation between differentiation of CRC, and colonic tumour expression of IL-38. IL-38 is a reliable/sensitive biomarker for distinguishing between CRC and non-cancer colonic tissue. There is a positive correlation between colonic IL-38 in CRC and prognosis and/or overall survival, particularly in advanced CRC, supporting IL-38 probably being a reliable and consistent independent factor in predicting the prognosis of CRC. The findings above may be useful in exploring therapeutic targeting for precision medicine.

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This work is supported by SJTU 2019, the University of Sydney (SB).

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  1. Shisan Bao and Rong Hu contributed equally to this work.

Authors and Affiliations

  1. Discipline of Pathology, School of Medical Sciences and Bosch Institute, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia

    Shisan Bao & Brett D. Hambly

  2. Discipline of Anesthesiology, School of Medicine, Hunan University of Medicine, Changsha, China

    Rong Hu

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  1. Shisan Bao
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  2. Rong Hu
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Correspondence to Shisan Bao.

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Bao, S., Hu, R. & Hambly, B.D. IL-34, IL-36 and IL-38 in colorectal cancer—key immunoregulators of carcinogenesis. Biophys Rev 12, 925–930 (2020). https://doi.org/10.1007/s12551-020-00726-0

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