Abstract
Pancreatic cancer is a devastating disease with dismal prognosis. The tumor microenvironment is composed by multiple cell types, molecular factors, and extracellular matrix forming a strong desmoplastic reaction, which is a hallmark of the disease. A complex cross-talk between tumor cells and the stroma exists with reciprocal influence that dictates tumor progression and ultimately the clinical outcome. In this context, tumor infiltrating immune cells through secretion of chemokine and cytokines exert an important regulatory role. Here we review the correlation between the immune infiltrates, evaluated on tumor samples of pancreatic cancer patients underwent surgical resection, and disease free and/or overall survival after surgery. Specifically, we focus on tumor infiltrating lymphocytes (TILs), mast cells (MCs) and macrophages that all contribute to a Th2-type inflammatory and immunosuppressive microenvironment. In these patients tumor immune infiltrates not only do not contribute to disease eradication but rather the features of Th2-type inflammation and immunosuppression is significantly associated with more rapid disease progression and reduced survival.
Highlights
A relationship between tumors and immune system exists (Schreiber et al, 2011)
We focus on tumor infiltrating lymphocytes (TILs), mast cells (MCs) and macrophages that all contribute to a Th2-type inflammatory and immunosuppressive microenvironment
At early stages immunosurveillance is responsible for tumor rejection (Elimination phase), in advanced stages the immune system prevents tumor outgrowth and edits tumor immunogenicity (Equilibrium phase) with the appearance in late stages of tumor cell variants that are no longer recognized by the immune system but rather tumors develop strategies to redirect infiltrating immune cells toward a pro-tumorigenic phenotype (Escape phase) (Dunn et al, 2004; Schreiber et al, 2011)
Summary
A relationship between tumors and immune system exists (Schreiber et al, 2011). multistep carcinogenesis results from a cross-talk between cancer-cell-intrinsic factors and host immune system (cell-extrinsic) effects (Zitvogel et al, 2006). We review the correlation between the immune infiltrates, evaluated on tumor samples of pancreatic cancer patients underwent surgical resection, and disease free and/or overall survival after surgery. In a large retrospective study of 212 tumor samples, the same Authors (Ino et al, 2013) reported that in multivariate analysis the prevalence of tumor infiltrating CD4+ Thigh/CD8+ Thigh/%Treglow significantly correlated with longer survival and had a higher hazard ratio.
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