Purpose: We developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts and explored its prognostic value in hepatocellular carcinoma (HCC).Experimental Design: The SII was developed based on a retrospective study of 133 patients with HCC undergoing resection between 2005 and 2006, and validated in a prospective study of 123 patients enrolled from 2010 to 2011. The circulating tumor cell (CTC) level in the validation cohort was measured using the CellSearch system. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUC).Results: An optimal cutoff point for the SII of 330 Â 10 9 stratified the patients with HCC into high (!330) and low SII (<330) groups in the training cohort. Univariate and multivariate analyses revealed the SII was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative a-fetoprotein and Barcelona Clinic Liver Cancer stage 0þA. The AUCs of the SII for survival and recurrence were higher than other conventional clinical indices. An SII ! 330 was significantly associated with vascular invasion, large tumors, and early recurrence. CTC levels were significantly higher in the SII ! 330 group (1.71 AE 0.34 vs. 4.37 AE 1.04, P ¼ 0.029). In patients with detectable CTCs, those with SII ! 330 had higher recurrence rates and shorter survival time than patients with SII < 330. Conclusion:The SII was a powerful prognostic indicator of poor outcome in patients with HCC and is a promising tool for HCC treatment strategy decisions. The dismal outcome in patients with high SII scores might be related to higher CTC levels. Clin Cancer Res; 20(23); 6212-22. Ó2014 AACR.

Inflammation is a fundamental innate immune response to perturbed tissue homeostasis. Chronic inflammatory processes affect all stages of tumour development as well as therapy. In this Review, we outline the principal cellular and molecular pathways that coordinate the tumour-promoting and tumour-antagonizing effects of inflammation and we discuss the crosstalk between cancer development and inflammatory processes. In addition, we discuss the recently suggested role of commensal microorganisms in inflammation-induced cancer and we propose that understanding this microbial influence will be crucial for targeted therapy in modern cancer treatment.

Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer (CRC)1. This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. IL-22, a cytokine of the IL-10 superfamily, plays an important role for colonic epithelial cell repair, and is increased in the blood and intestine of IBD patients2, 3. This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, IL-22RA2), however the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown4, 5. We describe herein that IL-22BP plays a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells (DC) in the colon in steady state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent down regulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumor development if uncontrolled during the recovery phase.Thus the IL-22-IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.

Highlights d Lung cancer development is associated with local dysbiosis and inflammation d Depletion of commensal microbiota suppresses lung adenocarcinoma development d Microbiota drive proliferation and activation of Vg6 + Vd1 + T cells in lung cancer d gd T cells promote neutrophil infiltration and tumor cell proliferation