Ectopic lymphoid-like structures (ELS) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicate poor prognosis in hepatocellular carcinoma (HCC). We studied an HCC mouse model, displaying abundant ELSs and found that they constitute immunopathological microniches, wherein progenitor malignant hepatocytes appear and thrive in a complex cellular and cytokine milieu until gaining self-sufficiency. Progenitor egression and tumor formation is associated with autocrine production of cytokines previously provided by the niche. ELSs develop upon cooperation between the innate and adaptive immune system which is facilitated by NF-κB activation and abolished by T cell depletion. These aberrant immune foci could be new targets for cancer therapy.

F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.

SUMMARY Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, reverse-engineering precision cancer prevention.

The preoperative prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer who are undergoing primary tumor resection. Investigation of the nutritional and immunologic statuses using the prognostic nutritional index could be a useful clinical approach.