ART TK Cancer and the chapter 22 Immune system S THE DEATH TOLL FROM INFECTIOUS DISEASE has declined in the Western world, cancer has become the second-ranking cause of death there. led only by heart disease. Current estimates project that one person in three in the United States will develop cancer, that one in five will die from it. From an immunologic per spective, cancer cells can be viewed as altered self-cells that have escaped normal growth-regulating mechanisms. This chapter examines the unique properties of cancer cells, pay. ing particular attention to those properties that can be recog- Cancerous melanoma cells nized by the immune system. The immune responses that develop to cancer cells, as well as the methods by which can cers manage to evade those responses, are then described. Cancer: Origin and Terminolo The final section describes current clinical and experimental a Malignant Transformation of Cells unotherapies for cancer. Oncogenes and Cancer Induction a Tumors of the Immune System Cancer: Origin and Terminology s Tumor Antigens In most organs and tissues of a mature animal, a balance is Immune Response to Tumors usually maintained between cell renewal and cell death. The Tumor Evasion of the Immune System various types of mature cells in the body have a given life span: as these cells die, new cells are generated by the prolif- Cancer Immunotherapy eration and differentiation of various types of stem cells. Under normal circumstances, the production of new cells is regulated so that the number of any particular type of cell constant. Occasionally, though, cells arise that longer respond to normal growth-control mechanisms. These cells give rise to clones of cells that can expand to a consider- of cancers of the colon, breast, prostate, and lung are carci- able size, producing a tumor, or neoplasm. nomas. The leukemias and lymphomas are malignant tu- A tumor that is not capable of indefinite growth and does mors of hematopoietic cells of the bone marrow and ac- not invade the healthy surrounding tissue extensively is be- count for about 9% of cancer incidence in the United States nign. a tumor that continues to grow and becomes progres- Leukemias proliferate as single cells, whereas lymphomas sively invasive is malignant; the term cancer refers speci- tend to grow as tumor masses. Sarcomas, which arise less fically to a malignant tumor. In addition to uncontrolled frequently (around 1% of the incidence in the United States) growth, malignant tumors exhibit metastasis; in this pro- are derived from mesodermal connective tissues such as ess, small clusters of cancerous cells dislodge from a tumor, bone, fat, and cartilage evade the blood or lymphatic vessels, and are carried to other tissues, where they continue to proliferate. In this way a primary tumor at one site can give rise to a secondary Malignant Transformation of Cells Malignant tumors or cancers are classified according to Treatment of normal cultured cells with chemical carcino- he embryonic origin of the tissue from which the tumor is gens, irradiation, and certain viruses can alter their mor derived. Most(>80%)are carcinomas, tumors that arise phology and growth properties. In some cases this process from endodermal or ectodermal tissues such as skin or the referred to as transformation, makes the cells able to pro- epithelial lining of internal organs and glands. The majority duce tumors when they are injected into animals. Such cells■ Cancer: Origin and Terminology ■ Malignant Transformation of Cells ■ Oncogenes and Cancer Induction ■ Tumors of the Immune System ■ Tumor Antigens ■ Immune Response to Tumors ■ Tumor Evasion of the Immune System ■ Cancer Immunotherapy Cancerous melanoma cells. Cancer and the Immune System A       has declined in the Western world, cancer has become the second-ranking cause of death there, led only by heart disease. Current estimates project that one person in three in the United States will develop cancer, and that one in five will die from it. From an immunologic per￾spective, cancer cells can be viewed as altered self-cells that have escaped normal growth-regulating mechanisms. This chapter examines the unique properties of cancer cells, pay￾ing particular attention to those properties that can be recog￾nized by the immune system. The immune responses that develop to cancer cells, as well as the methods by which can￾cers manage to evade those responses, are then described. The final section describes current clinical and experimental immunotherapies for cancer. Cancer: Origin and Terminology In most organs and tissues of a mature animal, a balance is usually maintained between cell renewal and cell death. The various types of mature cells in the body have a given life span; as these cells die, new cells are generated by the prolif￾eration and differentiation of various types of stem cells. Under normal circumstances, the production of new cells is regulated so that the number of any particular type of cell remains constant. Occasionally, though, cells arise that no longer respond to normal growth-control mechanisms. These cells give rise to clones of cells that can expand to a consider￾able size, producing a tumor, or neoplasm. A tumor that is not capable of indefinite growth and does not invade the healthy surrounding tissue extensively is be￾nign. A tumor that continues to grow and becomes progres￾sively invasive is malignant; the term cancer refers speci￾fically to a malignant tumor. In addition to uncontrolled growth, malignant tumors exhibit metastasis; in this pro￾cess, small clusters of cancerous cells dislodge from a tumor, invade the blood or lymphatic vessels, and are carried to other tissues, where they continue to proliferate. In this way a primary tumor at one site can give rise to a secondary tumor at another site (Figure 22-1). Malignant tumors or cancers are classified according to the embryonic origin of the tissue from which the tumor is derived. Most (>80%) are carcinomas, tumors that arise from endodermal or ectodermal tissues such as skin or the epithelial lining of internal organs and glands. The majority of cancers of the colon, breast, prostate, and lung are carci￾nomas. The leukemias and lymphomas are malignant tu￾mors of hematopoietic cells of the bone marrow and ac￾count for about 9% of cancer incidence in the United States. Leukemias proliferate as single cells, whereas lymphomas tend to grow as tumor masses. Sarcomas, which arise less frequently (around 1% of the incidence in the United States), are derived from mesodermal connective tissues such as bone, fat, and cartilage. Malignant Transformation of Cells Treatment of normal cultured cells with chemical carcino￾gens, irradiation, and certain viruses can alter their mor￾phology and growth properties. In some cases this process, referred to as transformation, makes the cells able to pro￾duce tumors when they are injected into animals. Such cells chapter 22 ART TK