Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant

Overwijk, Willem W.; Visser, Karin E. de; Tirion, Felicia H.; Jong, Laurina A. de; Pols, Thijs W.H.; Velden, Yme U. van der; Boorn, Jasper G. van den; Keller, Anna M.; Buurman, Wim A.; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B.A.G.

doi:10.4049/jimmunol.176.9.5213

Cited by 77 publications

(62 citation statements)

References 72 publications

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“…In this context, it has been reported that proinflammatory cytokines, including IL-17A, IL-6, and IL-23, can impair CD8 þ T-lymphocyte-mediated immune surveillance and promote de novo carcinogenesis and tumor neovascularization (29)(30)(31). In contrast, other groups have shown that IL-23 exerts antitumor activity through stimulation of T cells and NK cells (32)(33)(34)(35)(36)(37).…”

Section: Interleukin-23mentioning

confidence: 88%

Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

Giuliani

Airoldi

2011

Clinical Cancer Research

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Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic features of plasmablasts and/or plasma cells and usually localizes at multiple sites in the bone marrow. The pathogenesis of multiple myeloma is complex and dependent on the interactions between tumor cells and their microenvironment. Different cytokines, chemokines, and proangiogenic factors released in the tumor microenvironment are known to promote multiple myeloma cell growth. Here, we report recent advances on the role of 2 strictly related immunomodulatory cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic plasma cells, highlighting their ability to (i) act directly against multiple myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function. Finally, the therapeutic implication of these studies is discussed.

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Section: Interleukin-23mentioning

confidence: 88%

Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

Giuliani

Airoldi

2011

Clinical Cancer Research

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“…Several recent reports have indicated that IL-23 can mediate potent anti-tumor and anti-metastatic activity in murine models of cancer, in some cases equally as well as IL-12 [98]. Furthermore, when administered in combination with a gp100 peptide vaccine, IL-23 specifically increased the number of vaccine-induced CD8 + T cells and their production of IFN-γ [99]. Similarly, IL-27 potently enhances various aspects of T and/or NK cell function in vitro including enhancement of proliferative responses and the production of IFN-γ [100].…”

Section: Conclusion and Expert Opinionmentioning

confidence: 98%

Immunotherapy of cancer by IL-12-based cytokine combinations

Weiss

Subleski

Wigginton

et al. 2007

Expert Opinion on Biological Therapy

204

121

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Cancer is a multi-faceted disease comprising complex interactions between neoplastic and normal cells. Over the past decade, there has been considerable progress in defining the molecular, cellular and environmental contributions to the pathophysiology of tumor development. Despite these advances, the conventional treatment of patients still generally involves surgery, radiotherapy and/ or chemotherapy and the clinical outcome for many of these efforts remains unsatisfactory. Recent studies have highlighted the feasibility of using immunotherapeutic approaches that seek to enhance host immune responses to developing tumors. These strategies include immunomodulatory cytokines, with tumor necrosis factor (TNF) alpha, type I or type II Interferons (IFNs), Interleukins (IL)-2, IL-12, IL-15 and IL-18 being among the most potent inducers of anti-tumor activity in a variety of pre-clinical studies. More recently, some exciting new cytokines have been characterized, such as IL-21, IL-23, IL-27, and their immunomodulatory and anti-tumor effects in vitro and in vivo suggest that they may have considerable promise for future immunotherapy protocols. The promise of cytokine therapy does indeed derive from the identification of these novel cytokines, but even more fundamentally, the field is greatly benefiting from the ever-expanding amount of preclinical data that convincingly demonstrate synergistic and/or novel biological effects that may be achieved through the use of several combinations of cytokines with complementary immunestimulating capabilities. One cytokine in particular, IL-12, holds considerable promise by virtue of the fact that it plays a central role in regulating both innate and adaptive immune responses, can by itself induce potent anti-cancer effects, and synergizes with several other cytokines for increased immunoregulatory and anti-tumor activities. This review will discuss the anti-tumor activity of IL-12, with a special emphasis on its ability to synergize with other cytokines for enhancement of immune effector cell populations and regulation of host-tumor cell interactions and the overall tumor microenvironment.

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“…And in fact, elimination of IL-23 led to increased infiltration of CTL, rendering a protective effect against chemically-induced murine carcinogenesis [23]. Paradoxically, high levels of exogenous IL-23 have also been associated with a beneficial response [24,25], a discrepancy to be resolved.…”

Section: Tgf-β In Immune Dysregulationmentioning

confidence: 99%