Tumor Cyclooxygenase-2 Gene Suppresses Local Immune Responses in Patients with Hepatocellular Carcinoma

Iwamoto, Akemi; Ikeguchi, Masahide; Matsumoto, Sachico; Hukumoto, Youji; Inoue, Masashi; Ozaki, Tomohiro; Ataka, Masayuki; Tanida, Takashi; Endo, Kenji; Katano, Kuniyuki; Hirooka, Yasuaki

doi:10.1177/030089160609200208

Cited by 11 publications

(7 citation statements)

References 17 publications

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“…Indeed, such effects have already been shown in a murine Lewis lung carcinoma (3LL) model [107]. Recently, it has been described that COX-2 overexpression seems to be correlated with the suppression of local immune responses in HCCs, as the density of CD8-positive T cells was found to be decreased in COX-2-expressing tissue compared to non-COX-2-expressing tissue [108]. Although this study was solely descriptive, it might, however, be conceivable to translate an analogous scenario as was observed for NSCLC cells [107] to HCC cells.…”

Section: Modulation Of Immune Responsesmentioning

confidence: 94%

Cyclooxygenase-2 (COX-2) - A Therapeutic Target in Liver Cancer?

Breinig¹,

Schirmacher²,

Kern

2007

CPD

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Targeting COX-2, a key-enzyme of the prostaglandin metabolism, for the treatment of cancer has been in the focus of researchers for about a decade. However, only recently has this topic been related to hepatocellular carcinoma (HCC). HCC is one of the most common cancers and a growing health problem worldwide. At present, only few promising treatment options are available, accentuating the urgent need for novel therapeutic approaches. Since the first report of COX-2 overexpression in HCC, several findings support the notion that selective COX-2 inhibition proves to be beneficial in this malignancy. This review focuses on recent discoveries regarding the pro-tumorigenic potential of COX-2 in HCC and the functional effects of COX-2 inhibition on molecular mechanisms of this malignancy. Of clinical interest, promising data from in vivo experiments and case studies suggest a beneficial effect of COX-2 inhibitors for HCC- therapy. Detailed analysis of COX-2- activated pathways and related mechanisms may enable the evaluation and design of even more specific and combinatorial treatment approaches in the future.

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Section: Modulation Of Immune Responsesmentioning

confidence: 94%

Cyclooxygenase-2 (COX-2) - A Therapeutic Target in Liver Cancer?

Breinig¹,

Schirmacher²,

Kern

2007

CPD

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“…Elevation of the COX-2 was correlated with the suppression of local immune responses and early tumor recurrence in the residual liver in patients after resection (174)…”

Section: Figures and Tablesmentioning

confidence: 99%

Inflammation and cancer: how friendly is the relationship for cancer patients?

Aggarwal¹,

Gehlot²

2009

Current Opinion in Pharmacology

356

279

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Evidence has emerged in the last two decades that at the molecular level most chronic diseases, including cancer, are caused by a dysregulated inflammatory response. The identification of transcription factors such as NF-kB, AP-1 and STAT3 and their gene products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines, cyclooxygenase-2, 5 lipooxygenase, matrix metalloproteases, and vascular endothelial growth factor, adhesion molecules and others have provided the molecular basis for the role of inflammation in cancer. These inflammatory pathways are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, which together account for as much as 95% of all cancers. These pathways have been implicated in transformation, survival, proliferation, invasion, angiogenesis, metastasis, chemoresistance, and radioresistance of cancer, so much so that survival and proliferation of most types of cancer stem cells themselves appear to be dependent on the activation of these inflammatory pathways. Most of this evidence, however, is from preclinical studies. Whether these pathways have any role in prevention, progression, diagnosis, prognosis, recurrence or treatment of cancer in patients, is the topic of discussion of this review. We present evidence that inhibitors of inflammatory biomarkers may have a role in both prevention and treatment of cancer.

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“…Therefore, COX-2 can affect many pathways, which can also lead to immune suppression in cancer patients. Iwamoto et al have compared the expression level of COX-2 with the density of infiltrating T cells in HCC tumors and saw a lower CD8 + T-cell density in COX-2 expressing tumors compared with nonexpressing tumors [103]. They also concluded that COX-2 expression in the HCC tumor correlates with poor prognosis and a poor disease-free survival rate.…”

Section: Suppressive Factors Overexpressed In Hccmentioning

confidence: 99%

Immunotherapy of hepatocellular carcinoma

Korangy

Höchst

Manns

et al. 2010

Expert Review of Gastroenterology & Hepatology

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Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related death worldwide and efficient treatment options are urgently needed. Based on its pathogenesis, in addition to a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape mechanisms, including the generation of cells with immune suppressor functions, such as Tregs and myeloid-derived suppressor cells. It has been shown that these suppressor cells mask tumor-specific immune responses in patients with HCC. Different immunotherapeutic approaches including peptide- and dendritic cell-based therapies have demonstrated promising results in patients with HCC. However, we propose that any of these immunotherapeutic approaches needs to be combined with a therapy specifically targeting suppressor cells in HCC.

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Tumor Cyclooxygenase-2 Gene Suppresses Local Immune Responses in Patients with Hepatocellular Carcinoma

Cited by 11 publications

References 17 publications

Cyclooxygenase-2 (COX-2) - A Therapeutic Target in Liver Cancer?

Cyclooxygenase-2 (COX-2) - A Therapeutic Target in Liver Cancer?

Inflammation and cancer: how friendly is the relationship for cancer patients?

Immunotherapy of hepatocellular carcinoma

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