19.5 Cancer immunobiology and immunotherapy

Learning objectives

• Explain how the adaptive specific immune response responds to tumors
• Discuss the risks and benefits of tumor vaccines

Cancer involves a loss of the ability of cells to control their cell cycle , the stages each eukaryotic cell goes through as it grows and then divides. When this control is lost, the affected cells rapidly divide and often lose the ability to differentiate into the cell type appropriate for their location in the body. In addition, they lose contact inhibition and can start to grow on top of each other. This can result in formation of a tumor . It is important to make a distinction here: The term “ cancer ” is used to describe the diseases resulting from loss of cell-cycle regulation and subsequent cell proliferation. But the term “tumor” is more general. A “tumor” is an abnormal mass of cells, and a tumor can be benign (not cancerous) or malignant (cancerous).

Traditional cancer treatment uses radiation and/or chemotherapy to destroy cancer cells; however, these treatments can have unwanted side effects because they harm normal cells as well as cancer cells. Newer, promising therapies attempt to enlist the patient’s immune system to target cancer cells specifically. It is known that the immune system can recognize and destroy cancerous cells, and some researchers and immunologists also believe, based on the results of their experiments, that many cancers are eliminated by the body’s own defenses before they can become a health problem. This idea is not universally accepted by researchers, however, and needs further investigation for verification.

Cell-mediated response to tumors

Cell-mediated immune responses can be directed against cancer cells, many of which do not have the normal complement of self-proteins, making them a target for elimination. Abnormal cancer cells may also present tumor antigen s. These tumor antigens are not a part of the screening process used to eliminate lymphocytes during development; thus, even though they are self-antigens, they can stimulate and drive adaptive immune responses against abnormal cells.

Presentation of tumor antigens can stimulate naïve helper T cells to become activated by cytokines such as IL-12 and differentiate into T _H 1 cell s. T _H 1 cells release cytokines that can activate natural killer (NK) cells and enhance the killing of activated cytotoxic T cell s. Both NK cell s and cytotoxic T cells can recognize and target cancer cells, and induce apoptosis through the action of perforin s and granzyme s. In addition, activated cytotoxic T cells can bind to cell-surface proteins on abnormal cells and induce apoptosis by a second killing mechanism called the CD95 (Fas) cytotoxic pathway .

Despite these mechanisms for removing cancerous cells from the body, cancer remains a common cause of death. Unfortunately, malignant tumors tend to actively suppress the immune response in various ways. In some cancers, the immune cells themselves are cancerous. In leukemia , lymphocytes that would normally facilitate the immune response become abnormal. In other cancers, the cancerous cells can become resistant to induction of apoptosis . This may occur through the expression of membrane proteins that shut off cytotoxic T cells or that induce regulatory T cells that can shut down immune responses.