Not all tumors are made up of uniform cells, even if they originated from a single initiating cell. In some types of tumors, for example, only certain tumor cells, called cancer stem cells, are capable of seeding a new tumor. Within these tumors, some cells cease dividing, while others can continue cancerous growth. The latter, of course, are the most dangerous and the most important to destroy with anticancer treatments. Cancer stem cells are thought to give rise to some cells with high replicative capabilities and others with more limited replicative potential. The origins of these cancer stem cells are not clear. In some cancers, a normal tissue stem cell may give rise to the cancer stem cells. In others, dedifferentiation of terminally differentiated cells to form progenitor cells may give rise to cancer stem cells. Irrespective of their origin, cancer stem cells share gene expression signatures with normal tissue stem cells, leading to their designation as stem cell-like cells.

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The immediate environment of a tumor—the tumor microenvironment—contributes to the heterogeneity of cells within the tumor, influencing the behavior of the cancer stem cells and the tumor cells in general. Some neighboring cells may be more conducive to tumor growth than others. The importance of the tumor microenvironment extends to one of the most common environmental influences on a tumor cell: inflammatory cells. It is now widely accepted that cells of the immune system interact with the tumor. CD8⁺ cytotoxic T lymphocytes and natural killer cells surround and often migrate into the tumor, where they are thought to inhibit tumor formation. Mice deficient in these and other components of the immune system are more prone to carcinogen-induced tumors than normal mice. These findings lead to the idea that the immune system eliminates cancer cells. How cancer cells escape this immune surveillance is a critical question that remains to be addressed.

More and more evidence is mounting that immune-system cells can also have tumorigenic properties. It has been known for a long time that cancers frequently arise at sites of injury or chronic infection. It is estimated that up to 20 percent of cancers are linked to chronic infection. For example, persistent Helicobacter pylori infection is associated with gastric cancer. Crohn’s disease, an autoimmune disease that affects the intestines, is associated with colon cancer. Infection with hepatitis B or C viruses increases the risk of a form of liver cancer, hepatocellular carcinoma. Immune-system cells migrate to sites of injury or infection and produce growth factors, thereby stimulating tumor cell proliferation. They also produce factors to induce the growth of blood vessels, which—as we will discuss next—is an essential aspect of tumor growth and dissemination to distant sites.