Importance of tumor/stroma interactions in prognosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. It seems to be needed to find new ways to address the mechanisms involved in the progression of HCC, which can provide a prognostic evaluation and new therapeutic targets. Several studies have established that crosstalk between tumor cells and the microenvironment plays a key role in tumor progression and metastasis. In this context, the work of Zhu et al. contributes to assess interactions between tumor and microenvironment associated-macrophages promoting tumor progression and metastasis. Indeed, they concluded that the interplay of osteopontin (OPN) and peritumoral macrophages (PTMs) represents a new insight into tumor progression and therapeutic targets for HCC. Historically, tumor-infiltrating leukocytes have been considered to be manifestations of an intrinsic defensive mechanism against developing tumors, however, now, it is know that that leukocytes infiltration can promote tumor phenotypes, such as angiogenesis, growth, and invasion. Characterization of functional heterogeneity of stromal cell components, and specifically the analysis of stromal fibroblasts can provide a new focus on mechanisms involved in the progression of HCC. All of this opens the possibility to provide prognostic information for HCC based on biological parameters derived from peritumoral status from tumors.