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Review

IL-12 Family Cytokines in Cancer and Immunotherapy

1
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
2
Department of Genetics, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(2), 167; https://doi.org/10.3390/cancers13020167
Received: 1 December 2020 / Revised: 22 December 2020 / Accepted: 29 December 2020 / Published: 6 January 2021
(This article belongs to the Special Issue Challenges and Opportunities for Effective Cancer Immunotherapies)
The IL-12 family cytokines play an important role in regulating the tumor immune contexture. Recent efforts geared towards the development of better immune therapeutic approaches have identified the need to overcome immune suppression and improve the quantity and quality of anti-tumor effector immune cells within the tumor milieu. In this review, we summarize the recent findings on IL-12 family cytokines in regulating anti-tumor immunity as well as the effectiveness and benefits of enhancing anti-tumor immunity in pre-clinical and clinical settings by targeting IL-12 family cytokines.
The IL-12 family cytokines are a group of unique heterodimeric cytokines that include IL-12, IL-23, IL-27, IL-35 and, most recently, IL-39. Recent studies have solidified the importance of IL-12 cytokines in shaping innate and adaptive immune responses in cancer and identified multipronged roles for distinct IL-12 family members, ranging from effector to regulatory immune functions. These cytokines could serve as promising candidates for the development of immunomodulatory therapeutic approaches. Overall, IL-12 can be considered an effector cytokine and has been found to engage anti-tumor immunity by activating the effector Th1 response, which is required for the activation of cytotoxic T and NK cells and tumor clearance. IL-23 and IL-27 play dual roles in tumor immunity, as they can both activate effector immune responses and promote tumor growth by favoring immune suppression. IL-35 is a potent regulatory cytokine and plays a largely pro-tumorigenic role by inhibiting effector T cells. In this review, we summarize the recent findings on IL-12 family cytokines in the control of tumor growth with an emphasis primarily on immune regulation. We underscore the clinical implications for the use of these cytokines either in the setting of monotherapy or in combination with other conventional therapies for the more effective treatment of malignancies. View Full-Text
Keywords: IL-12 family cytokines; tumor microenvironment; cancer immunotherapy; anti-tumor immunity; STAT; B cell; T cell IL-12 family cytokines; tumor microenvironment; cancer immunotherapy; anti-tumor immunity; STAT; B cell; T cell
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MDPI and ACS Style

Mirlekar, B.; Pylayeva-Gupta, Y. IL-12 Family Cytokines in Cancer and Immunotherapy. Cancers 2021, 13, 167. https://doi.org/10.3390/cancers13020167

AMA Style

Mirlekar B, Pylayeva-Gupta Y. IL-12 Family Cytokines in Cancer and Immunotherapy. Cancers. 2021; 13(2):167. https://doi.org/10.3390/cancers13020167

Chicago/Turabian Style

Mirlekar, Bhalchandra, and Yuliya Pylayeva-Gupta. 2021. "IL-12 Family Cytokines in Cancer and Immunotherapy" Cancers 13, no. 2: 167. https://doi.org/10.3390/cancers13020167

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