CTLs and virus-associated tumors

CTLs and cancerous blood cells

Okay, so CTLs probably don’t provide serious surveillance against non-blood-cell, spontaneous tumors. That’s a real bummer, because these make up the majority of human tumors. But what about blood-cell cancers like leukemia and lymphoma? Maybe CTLs are useful against them. After all, immunosuppressed humans do have higher frequencies of leukemia and lymphoma than do humans with healthy immune systems. This suggests that there might be something fundamentally different about the way the immune system views tumors in tissues and organs versus the way it sees blood cells that have become cancerous. Let’s take a look at what these differences might be.

One of the problems that CTLs have in providing surveillance against tumors that arise in tissues is that these tumors simply are not on the normal traffic pattern of virgin T cells – and it’s hard to imagine how a CTL could be activated by a cancer it doesn’t see. In contrast, most blood-cell cancers are found in the blood, lymph, and secondary lymphoid organs, and this is ideal for viewing by CTLs, which pass through these areas all the time. Thus, in the case of blood-cell cancers, the traffic patterns of cancer cells and virgin T cells actually intersect. Moreover, in contrast to tumors in tissues, which usually are unable to supply the co-stimulation required for activation of virgin T cells, some cancerous blood cells actually express high levels of B7, and therefore can provide the necessary co-stimulation. These properties of blood-cell cancers suggest that CTLs may provide surveillance against some of them. Unfortunately, this surveillance must be incomplete, because people with otherwise healthy immune systems still get leukemias and lymphomas.

Certain viral infections can predispose a person to particular types of cancer. Because Mother Nature probably designed killer T cells to defend against viral infections, it is easy to imagine that CTLs might provide surveillance against virus-associated tumors. Unfortunately, this surveillance is probably quite limited. Here’s why. Most viruses cause “acute” infections in which all the virus-infected cells are rather quickly destroyed by the immune system. And because a dead cell isn’t going to make a tumor, viruses which only cause acute infections do not play a role in cancer. This explains why most viral infections are not associated with human cancer.

There are viruses, however, which can evade the immune system, and establish long-term (sometimes lifelong) infections. Importantly, all viruses which have been shown to play a role in causing cancer are able to establish long-lasting infections during which they “hide” from the immune system. Because CTLs cannot destroy virus-infected cells while they are hiding, and because these hidden cells are the very ones which eventually become cancer cells, it can be argued that CTLs do not provide effective surveillance against virus-associated cancer.

Of course, you might propose that without killer T cells, more cells would be infected during a virus attack, thereby increasing the number of cells in which the virus might be able to establish a long-term, hidden infection. And this probably is true. In fact, this may help explain why humans with deficient immune systems have higher than normal rates of virus-associated tumors. However, the bottom line is that CTLs cannot provide significant surveillance against virus-infected cells once they have become cancerous, because these cancers only result from long-term viral infections – infections which CTLs cannot detect or cannot deal with effectively.

Дата добавления: 2015-06-04