Serum Interleukin-10 But Not Interleukin-6 Is Related to Clinical Outcome in Patients With Resectable Hepatocellular Carcinoma

Chau, Gar‐Yang; Wu, Chew-Wun; Lui, Wing‐Yiu; Chang, Tsan‐Kuo; Kao, Hua-Li; Wu, Li‐Hwa; King, Kuang‐Liang; Loong, Che‐Chuan; Hsia, Chen-Yuang; Chi, Chin‐Wen

doi:10.1097/00000658-200004000-00015

Cited by 134 publications

(106 citation statements)

References 32 publications

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“…Our results echo a previous study indicating that the serum IL-10 level was an adverse prognostic factor for patients with HCC after surgical resection. 18 With respect to inoperable HCC, to our knowledge, there has only been 1 retrospective series based on 74 patients; in that series, it was demonstrated that a serum IL-10 level >10 pg/mL (ie, log IL-10 level >1 pg/mL) was a negative prognostic factor. 23 However, in that study, the independent prognostic significance of IL-10 was not determined by multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

Chan

Wong

et al. 2011

Cancer

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BACKGROUND: The level of circulating interleukin 10 (IL‐10) is elevated in a proportion of patients with hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the prognostic significance of serum the IL‐10 level in patients with unresectable HCC. METHODS: Patients with unresectable HCC who provided serum at the time of diagnosis were enrolled prospectively in the study. The level of circulating IL‐10 in serum samples was determined by enzyme‐linked immunosorbent assay. The association of the IL‐10 level with overall survival was evaluated in relation to sociodemographics, liver function, hepatitis B viral load, and tumor staging. RESULTS: In total, 222 patients were recruited; of these, 82.4% were positive for hepatitis B virus surface antigen, and 65.8% had Barcelona Clinic Liver Cancer stage C disease. The mean log IL‐10 level was 1.1 pg/mL, and 146 patients had an IL‐10 level >1 pg/mL (high IL‐10 group). The high IL‐10 group had worse overall survival than the low IL‐10 group (5.0 months vs 14.9 months; hazard ratio, 2.192; P < .0001). The IL‐10 level was associated with worse hepatic function and with a high alanine transaminase (ALT) level. The IL‐10 level remained an independent prognostic factor (hazard ratio, 1.824; P = .0005) after adjustment for sociodemographics, tumor staging, treatment, Child‐Pugh stage, and ALT level. The IL‐10 level also subdivided patients into 2 populations with distinct survival (10.2 months vs 3.5 months; P = .0027). CONCLUSIONS: The serum IL‐10 level was identified as an independent prognostic factor for unresectable HCC. The current findings suggested that an elevated IL‐10 level may be related to hepatic injury caused by cirrhotic processes rather than tumor load. The authors concluded that the IL‐10 level offers additional prognostic value to the existing tumor staging systems. Cancer 2012. © 2011 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

Chan

Wong

et al. 2011

Cancer

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“…The anti-infl ammatory characteristics of IL-10 downregulate the host immune response [25]. A high IL-10 level was suggested to contribute to a relative state of immunosuppression in patients with hepatocellular carcinoma [26]. Matsuguchi et al [27] reported that high serum IL-10 levels in patients with hepatocellular carcinoma presumably also resulted from the secretion of IL-10 by tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin-6 and -10 levels in patients with gastric cancer

et al. 2009

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“…Therefore, T-cell suppression derived from tumor-secreted IL-10 becomes one of the major barriers to T-cell immunotherapy of tumors. Clinically, the detectible serum IL-10 in cancer patients becomes a negative indicator for clinical outcome 17,18 TNF-a is a multifunctional cytokine with a broad spectrum of activities. It activates IL-2R/IFN-g expression and cytotoxicity of T cells, 19 and stimulates T-cell proliferation and activation 20 through activation of nuclear factor-kappa B (NF-kB) involving multiple cytokine activation.…”

Section: Introductionmentioning

confidence: 99%

Engineered CD8+ cytotoxic T cells with fiber-modified adenovirus-mediated TNF-α gene transfection counteract immunosuppressive interleukin-10-secreting lung metastasis and solid tumors

Shi

Chan

et al. 2007

Cancer Gene Ther

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T-cell suppression derived from tumor-secreted immunosuppressive interleukin (IL)-10 becomes a major barrier to CD8 þ T-cell immunotherapy of tumors. Tumor necrosis factor-alpha (TNF-a) is a multifunctional cytokine capable of activating T and dendritic cells (DCs) and counteracting IL-10-mediated DC inhibition and regulatory T-cell-mediated immune suppression. In this study, we constructed a recombinant adenovirus MF AdVTNF with fiber-gene modified by RGD insertion into the viral knob's H1 loop and a melanoma cell line B16 OVA/ILÀ10 engineered to express ovalbumin (OVA) and to secrete IL-10 (2.2 ng/ml/10 6 cells/24 h). We transfected OVA-specific CD8 þ T cells with MF AdVTNF, and found a fivefold increase in transgene human TNF-a secretion (4.3 ng/ ml/10 6 cells/24 h) by the engineered CD8 þ T TNF cells transfected with MF AdVTNF, compared to that (0.8 ng/ml/10 6 cells/24 h) by CD8 þ T cells transfected with the original AdVTNF without viral fiber modification. The engineered CD8 þ T TNF cells exhibited enhanced cytotoxicity and elongated survival in vivo after adoptive transfer. TNF-a derived from both the donor CD8 þ T cells and the host cells plays an important role in donor CD8 þ T-cell survival in vivo after adoptive transfer. We also demonstrated that the transfected B16 OVA/ILÀ10 tumor cells secreting IL-10 are more resistant to in vivo CD8 þ T-cell therapy than the original B16 OVA tumor cells without IL-10 expression. Interestingly, the engineered CD8 þ T TNF cells secreting transgene-coded TNF-a, but not the control CD8 þ T control cells without any transgene expression eradicated IL-10-secreting 12-day lung micrometastasis in all 10/10 mice and IL-10-secreting solid tumors (B5 mm in diameter) in 6/10 mice. Transfer of the engineered CD8 þ T TNF cells further induced both donor-and host-derived memory CD8 þ T cells, leading to a stronger long-term antitumor immunity against the IL-10-secreting B16 OVA/ILÀ10 tumor cell challenges. Therefore, CD8 þ T cells engineered to secrete TNF-a may be useful when designing strategies for adoptive T-cell therapy of solid tumors.

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Serum Interleukin-10 But Not Interleukin-6 Is Related to Clinical Outcome in Patients With Resectable Hepatocellular Carcinoma

Abstract: In patients with HCC, the preoperative serum IL-10 level is related to the clinical outcome. IL-10 may play an important role in the progression of HCC.

Cited by 134 publications

References 32 publications

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

Serum interleukin-6 and -10 levels in patients with gastric cancer

Engineered CD8+ cytotoxic T cells with fiber-modified adenovirus-mediated TNF-α gene transfection counteract immunosuppressive interleukin-10-secreting lung metastasis and solid tumors

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