The immunological contribution of NF-κB within the tumor microenvironment: a potential protective role of zinc as an anti-tumor agent

Abstract

Over decades, cancer treatment has been mainly focused on targeting cancer cells and not much attention to host tumor microenvironment. Recent advances suggest that the tumor microenvironment requires in-depth investigation for understanding the interactions between tumor cell biology and immunobiology in order to optimize therapeutic approaches. Tumor microenvironment consists of cancer cells and tumor associated reactive fibroblasts, infiltrating non-cancer cells, secreted soluble factors or molecules, and non-cellular support materials. Tumor associated host immune cells such as Th(1), Th(2), Th17, regulatory cells, dendritic cells, macrophages, and myeloid-derived suppressor cells are major components of the tumor microenvironment. Accumulating evidence suggests that these tumor associated immune cells may play important roles in cancer development and progression. However, the exact functions of these cells in the tumor microenvironment are poorly understood. In the tumor microenvironment, NF-κB plays an important role in cancer development and progression because this is a major transcription factor which regulates immune functions within the tumor microenvironment. In this review, we will focus our discussion on the immunological contribution of NF-κB in tumor associated host immune cells within the tumor microenvironment. We will also discuss the potential protective role of zinc, a well-known immune response mediator, in the regulation of these immune cells and cancer cells in the tumor microenvironment especially because zinc could be useful for conditioning the tumor microenvironment toward innovative cancer therapy.

Fig. 1

Schematic diagram of possible interactions between tumor cells, lymphoid, myeloid and stromal components involved in immune escape and tumor progression. Various cytokines and growth factors produced by tumors or stroma may recruit and activate several immune suppressive cells, resulting in tumor progression. (MDSC: myeloid derived suppressor; imDC: immature dendritic cells; mDC: mature dendritic cells; Treg: T regulatory cells; Teff: effector T cells; NK: natural killer cell; TAM: tumor associated macrophages).