Tumor Immunology. Tumor (latin) = swelling

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1 Tumor Immunology Tumor (latin) = swelling benign tumor malignant tumor Tumor immunology : the study of the types of antigens that are expressed by tumors how the immune system recognizes and responds to these antigens how the tumors evade the host immune system immunologic approaches to detecting, diagnosing, and treating cancers

2 Immune Surveillance Phenomenon 1950s Macfarlane Burnet Cancer cells arise frequently within the body One of the primary functions of the immune system is to eradicate such cells A tumor arises only if this surveillance mechanism fails for some reason

3 Immune Surveillance Phenomenon However tumor immunity is often weak and is easily overwhelmed by rapidly growing tumors. Tumor immunity varies with the type of tumor. Many tumors have specialized mechanisms for evading host immune responses.

4

5 Tumor Antigens A variety of tumor antigens that may be recognized by T and B lymphocytes have been identified in human and animal cancers. The classification of tumor antigens Past : tumor-specific antigens vs tumor-associated antigens Present : relies on the molecular structure and source of the antigens Examples of the main classes of tumor antigens Oncofetal antigens : tumor-associated antigens Products of oncogenic viruses Altered glycolipids and glycoproteins antigens

6 Oncofetal Antigens Carcinoembryonic antigen (CEA, CD66) an intercellular adhesion molecule high expression restricted to cells in the gut, pancreas, and liver during the 1 st two trimesters of gestation low expression in normal adults colonic mucosa and lactating breast expression is increased in CA of the colon, pancreas, stomach, and breast

7 CEA (ng/ml) CEA TUMOR ANTIGEN IN COLON CANCER Normal Range Surgical Removal of Tumor Time in Days Clinical Manifestations Appear

8 Oncofetal Antigens Alpha-fetoprotein (AFP) synthesized and secreted in fetal life by yolk sac and liver only low levels are present in adult serum significantly elevated in patients with hepatocellular carcinoma and germ cell tumors a useful indicator of advanced or recurrent liver or germ cell tumors

9 Products of Oncogenic Viruses DNA viruses are implicated in the development of tumors in humans and experimental animals Human papillomavirus E6 and E7 proteins (cervical carcinomas) EBNA-1 protein of Epstein-Barr virus (EBV-associated lymphomas, nasopharyngeal carcinoma) Hepatitis B virus is not oncogenic, but it promotes the development of liver cancer probably by inducing chronic inflammation The only human RNA tumor virus that known to cause tumors is human T cell lymphotropic virus 1 (HTLV-1) adult T cell leukemia/ lymphoma (ATL)

10 Altered Glycolipid and Glycoprotein Antigens Cancer antigen-125 (CA-125) a mucinous glycoprotein and marker for ovarian cancer also elevated in other malignant cancers, including those originating in the endometrium, fallopian tubes, lungs, breast and gastrointestinal tract approved for following the response to treatment, predicting prognosis after treatment and detecting the recurrence of ovarian cancer

11 Altered Glycolipid and Glycoprotein Antigens Cancer antigen 19-9 (CA 19-9) a mucinous glycoprotein elevated in cancer of the pancreas, colon, and bile ducts help differentiate between cancer of the pancreas and bile ducts and other non-cancerous conditions, such as pancreatitis monitor a patient's response to pancreatic cancer treatment watch for pancreatic cancer recurrence

12 Immune Responses to Tumors T lymphocytes : killing of tumor cells by CD8 + CTLs. A B

13

14 Tumor Infiltrating Lymphocyte

15 Antibodies

16 N a t u r a l K i l l e r C e l l s

17 Macrophages possibly activated by direct recognition of some surface antigens of tumor cells and by IFN-g produced by tumor-specific T cells. activated macrophages exhibit selective cytotoxicity against tumor cells kill by releasing lysosomal enzymes, reactive oxygen intermediates, nitric oxide or secretion of tumor necrosis factor (TNF)

18

19 Immunotherapy for Tumors Active immunotherapy vaccination with tumor cells and tumor antigens, dendritic cells incubated with tumor antigens or transfected with plasmid expressing tumor antigen

20

21 Enhancement of tumor cell immunogenicity by transfection of costimulator and cytokine genes

22 Nonspecific stimulation of the immune system stimulated by the local administration of inflammatory substances or by systemic treatment with agents that function as polyclonal activators activate macrophages or stimulate T cell responses bacillus Calmette-Guerin (BCG) : carcinoma of the bladder

23 Passive Immunotherapy

24 Adoptive cellular therapy Lymphokine-activated killer (LAK) cells

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