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Anticancer properties of the IL-12 family--focus on colorectal cancer.
- Source :
-
Current medicinal chemistry [Curr Med Chem] 2010; Vol. 17 (29), pp. 3303-8. - Publication Year :
- 2010
-
Abstract
- The prominent role of interleukin (IL)-12 in inflammatory responses, especially in TH1 T cell differentiation, is well established. Moreover, in murine models of tumorigenesis, IL-12 displays remarkable antitumor properties that are mainly mediated by interferon (IFN)-γ secretion by CD4+, CD8+ T cells, natural killer (NK) or NK-T cells. Importantly, IL-12 through IFN- γ -dependent induction of the antiangiogenic factors interferon-inducible protein (IP) 10 and monokine induced by gamma interferon (MIG) contributes to tumor eradication. Recently, the structurally similar but functionally different cytokines IL-23 and IL-27 were discovered and related to the IL-12 family of cytokines. Each of those cytokines has its own specific effects on tumor growth. Similarly to IL12p70, antitumor effects of IL-27 are mediated via the IFN γ -IP10/MIG-axis and tumor-specific increase of cytotoxic T-lymphocyte activity. Additionally, IL-27 itself may mimic the function of IFN- γ due to the similarity in usage of JAK/STAT signalling molecules such as STAT1. The role of IL-23 in tumor growth to date is controversial. Whether IL-23 acts pro- or anticancerogenic seems to depend on a critical balance of STAT3 signalling in both the tumor and the immune cellular microenvironment of the tumor. At least for solid tumors the promising results from preclinical studies of systemic and on-site IL-12-based therapy did not prevail in clinical studies. In future combinatorial approaches using IL-12 together with other cytokines or antiangiogenic molecules have to be evaluated. This review focuses on anticancer effects of the IL-12 family in preclinical and clinical studies with an emphasis on colorectal cancer.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents metabolism
Chemokine CXCL10 metabolism
Chemokine CXCL9 metabolism
Clinical Trials as Topic
Colorectal Neoplasms pathology
Drug Evaluation, Preclinical
Humans
Interleukin-12 chemistry
Interleukin-12 metabolism
Interleukin-23 chemistry
Interleukin-23 metabolism
Mice
T-Lymphocytes immunology
T-Lymphocytes metabolism
Antineoplastic Agents therapeutic use
Colorectal Neoplasms drug therapy
Interleukin-12 therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1875-533X
- Volume :
- 17
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Current medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20712574
- Full Text :
- https://doi.org/10.2174/092986710793176366