Immune Surveillance

Immune surveillance is a theory that the immune system patrols the body not only to recognize and destroy invading pathogens but also host cells that become cancerous. Perhaps potential cancer cells arise frequently throughout life, but the immune system usually destroys them as fast as they appear. There is some evidence for this attractive notion. There is also evidence that the immune system mounts an attack against established cancers although it often fails.

For immune surveillance to work, cancer cells must express antigens that are not found on normal cells. Otherwise the immune system would see them as "self" and be tolerant of them. Some examples of tumor antigens:

Immunodeficient Mice

Mice with genes needed to make Th1 cells and/or cytotoxic T lymphocytes (CTLs) and/or NK cells knocked out

Normal Mice

When mice with a normal immune system are given very low doses of a chemical carcinogen, a few develop rapidly-growing tumors but many do not. However, it turns out that malignant cells are present in the healthy animals as well, but something is holding them in check. That appears to be the adaptive immune system because, treating them with

causes fatal tumors to begin to grow in many of them.

Control animals treated with antibodies that did not target T-cells or their functions remained healthy.

Immunodeficient Humans

Humans with depressed immune systems, e.g., have an elevated incidence of cancers such as Kaposi's sarcoma (AIDS) and B-cell lymphomas (in both AIDS patients and transplant recipients).

A revealing example: Both recipients of a cadaver kidney from a woman, who had been seemingly cured of her melanoma 16 years before, developed melanomas that were genetically the woman's. The recipient's failure to reject those cells was because of the immunosuppressive measures they were receiving so as not to reject her kidney. She must have harbored melanoma cells all those years with her immune system keeping them in check.

Immunocompetent Humans

Cancer patients whose tumors contain large numbers of tumor-infiltrating lymphocytes (TILs), e.g., Th1 cells and/or cytotoxic T lymphocytes (CTLs) and/or NK cells cope with their disease better than patients with only small numbers of these cells.

Why Does Immune Surveillance Fail?

Perhaps most of the time it doesn't. Perhaps visible cancers represent a rare failure of a system that has been eliminating transformed cells throughout life.

But if that is true, what led to the rare failures?

If a cell succeeds in starting down the path leading to uncontrolled mitosis [Link], it may acquire somatic mutations that increasingly protect it from attack by the host's immune system. Examples:

Whatever the importance of the body's innate response to cancer cells, there is no longer any question that the immune system can be manipulated to help against tumors. Some of the methods employed are described on a separate page: Cancer Immunotherapy.

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27 September 2019