Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala, Manohar Babu; Syed, Sunayana Begum; Bandaru, Srinivas; Varre, Sreedevi; Jyothy, A.; Mundulru, Hema Prasad

doi:10.7314/apjcp.2012.13.11.5353

Cited by 19 publications

(18 citation statements)

References 78 publications

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“…Conversely, Kuppala et al . showed that IL-18 was an immune-stimulatory cytokine with antitumor activity in preclinical models, and could be a useful candidate in gene therapy of lymphoma or lymphoid leukemia26. The physiological roles of IL-37, a newly identified IL-1 family member, in tumors, were unclear.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-37 Mediates the Antitumor Activity in Hepatocellular Carcinoma: Role for CD57+ NK Cells

Zhao

Pan

et al. 2014

Sci Rep

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The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues, and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues was positively associated with the density of tumor-infiltrating CD57+ natural killer (NK) cells, but not with the CD3+ and CD8+ T cells. Consistently, in vitro chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit more NK cells. The in vivo mouse model experiments also revealed that overexpression IL-37 in HCC cells significantly delayed tumor growth and recruited more NK cells into tumors tissues. Our finding suggested that IL-37 might play an important role for the prognosis of HCC patients via regulating innate immune-action.

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Section: Discussionmentioning

confidence: 99%

Interleukin-37 Mediates the Antitumor Activity in Hepatocellular Carcinoma: Role for CD57+ NK Cells

Zhao

Pan

et al. 2014

Sci Rep

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“…Systemic administration of IL-18 has been shown to result in a significant antitumor immune activity in several preclinical animal models. 70 The ɣ-chain family of cytokines includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. IL-2 is a key growth factor involved in the clonal expansion of antigen-activated lymphocytes and the generation of immune memory.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

Селедцов

Гончаров

Селедцова

2015

Human Vaccines & Immunotherapeutics

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“…It is synthesized as a 24-kDa precursor protein, cleaved into an 18-kDa mature form by caspase-1, and then secreted (3). IL18 is produced mainly by immune cells and effectively enhances innate and adaptive immune responses (4).…”

Section: Introductionmentioning

confidence: 99%

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

Guo

Jiang

et al. 2016

Clinical Cancer Research

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Purpose: We sought to find new immune-based treatments for pancreatic cancer.Experimental Design: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms.Results: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-kB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-kB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice.Conclusions: IL18 has both cancer-promoting and cancersuppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-kB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-kB pathway.

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Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Cited by 19 publications

References 78 publications

Interleukin-37 Mediates the Antitumor Activity in Hepatocellular Carcinoma: Role for CD57+ NK Cells

Interleukin-37 Mediates the Antitumor Activity in Hepatocellular Carcinoma: Role for CD57+ NK Cells

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

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