The tumor microenvironment

Abstract

A tumor is not simply a group of cancer cells, but rather a heterogeneous collection of infiltrating and resident host cells, secreted factors and extracellular matrix. Tumor cells stimulate significant molecular, cellular and physical changes within their host tissues to support tumor growth and progression. An emerging tumor microenvironment is a complex and continuously evolving entity. The composition of the tumor microenvironment varies between tumor types, but hallmark features include immune cells, stromal cells, blood vessels, and extracellular matrix. It is believed that the "tumor microenvironment is not just a silent bystander, but rather an active promoter of cancer progression" (Truffi et al., 2020). Early in tumor growth, a dynamic and reciprocal relationship develops between cancer cells and components of the tumor microenvironment that supports cancer cell survival, local invasion and metastatic dissemination. To overcome a hypoxic and acidic microenvironment, the tumor microenvironment coordinates a program that promotes angiogenesis to restore oxygen and nutrient supply and remove metabolic waste. Tumors become infiltrated with diverse adaptive and innate immune cells that can perform both pro- and anti- tumorigenic functions (Figure 1). An expanding literature on the tumor microenvironment has identified new targets within it for therapeutic intervention.

Figure 1.. Impact of immune cells within the TME.

The role of immune cells in the TME can be to either suppress tumor formation (anti-tumor microenvironment) or promote tumorigenesis (immune suppressive microenvironment). Depending on context and tumor type immune cells can both be pro or anti-tumorigenic.

Figure 2.. Defining the role of stromal cells in promoting cancer progression.

Cancer cells recruit stromal cells from neighboring tissue during tumorigenesis. In the TME, stromal cells and cancer are in a dynamic relationship promoting the cancer progression. The stromal cell composition varies between tumor types but includes endothelial cells, fibroblasts, adipocytes and stellate cells. The TME orchestrates angiogenesis, proliferation, invasion and metastasis through the secretion of growth factors and cytokines.