M10 Tumor Immunology

• Cancer is a major health problem worldwide and one of the most important causes of morbidity and mortality in children and adults
• Malignant phenotype of cancers


  • Defective regulation of cell proliferation
  • Resistance of the tumor cells to apoptotic death
  • Ability of the tumor cells to invade host tissues and metastasize to distant sites
  • Ability of tumor cells to evade host immune defense mechanisms
• In this module, we will describe the types of antigens that are expressed by malignant tumors, how the immune system recognizes and responds to these antigens, how tumors evade the host immune system, and the application of immunologic approaches to the treatment of cancer
• Tumor immunology


  The study of the relationship between the immune system and cancer cells
• Areas of tumor immunology

  • The antigens associated with tumor cells
  • The host's immune responses to tumors
  • Mechanisms by which tumors are thought to escape these responses
  • Therapeutic use of the immune system in an attempt to eradicate tumors
• Tumor


  An abnormal cell mass (from the Latin, meaning "to swell") or neoplasm (from the Greek, meaning "new growth")
• Benign tumors


  • Named by adding suffix -oma to the name of the cells of origin
  • Exception to this rule are lymphomas, melanomas, hepatomas
• Types of malignant tumors

  • Carcinomas (80%)
  • Leukemias or lymphomas (9%)
  • Sarcomas (1%)
• Tumor-specific antigens (TSAs)


  Unique to the tumor of an individual patient or shared by a limited number of patients with the same type of tumor, coded for by viral oncogenes, host proto-oncogenes or tumor suppressor genes that have undergone genetic mutations
• Tumor-associated antigens (TAAs)


  Expressed in normal cells as well as in tumor cells, but abnormally expressed in terms of their concentration, location, or stage of differentiation
• Types of TAAs


  • Shared TSAs
  • Differentiation antigens
  • Overexpressed antigens
• Shared TSAs


  Expressed in many tumors, but not in most normal tissues, except testicular germ cells, placental trophoblasts and ovaries
• Differentiation antigens


  Expressed on immature cells of a particular lineage, including oncofetal or embryonic antigens like CEA, AFP, and PSA
• Overexpressed antigens


  Found in higher levels on malignant cells than on normal cells, due to genetic mutations that deregulate their expression
• Tumor markers


  Biological substances found in increased amounts in the blood, body fluids, or tissues of patients with a specific type of cancer
• Types of tumor markers

  • Proteins
  • Carbohydrates
  • Oncofetal antigens
  • Hormones
  • Metabolites
  • Receptors
  • Enzymes
• Characteristics of an ideal tumor marker

  • Produced by the tumor itself or by the patient's body in response to the tumor
  • Secreted into a biological fluid, where it can be inexpensively and easily quantified
  • Have a circulating half-life long enough to permit its concentration to rise with increasing tumor load
  • Increase to clinically significant levels above the reference level while the disease is still treatable
  • Have a high sensitivity
  • Have a high specificity
• Clinical uses of tumor markers

  • Screening of tumors
  • Diagnosing tumors
  • Assessing the prognosis of the patient
  • Monitoring of patient's response to treatment
• The detection of tumor markers provides an ideal way to screen for tumors because the markers can be detected by a simple blood test
• Tumor markers can serve as a valuable aid in making a cancer diagnosis when they are used in conjunction with clinical findings and other tests, but they are not diagnostic by themselves
• A high concentration of a tumor marker at the time of diagnosis or increasing levels of a tumor marker over time can indicate the presence of an aggressive tumor that has metastasized and requires rigorous treatment
• A significant decrease in the concentration of a tumor marker after surgery, chemotherapy, or other treatment indicates that the therapy has been effective in shrinking the tumor. In contrast, an increasing level of the marker after a return to normal, indicates that the tumor has recurred and that more aggressive treatment may be needed
• Common tumor markers


  • Alpha-fetoprotein (AFP)
  • β2-microglobulin
  • Calcitonin and Serum Calcium (Ca++)
• Common Tumor Markers


  • Alpha-fetoprotein (AFP)
  • β2– microglobulin
  • Calcitonin and Serum Calcium (Ca++)
  • CD markers
  • Carcinoembryonic antigen (CEA)
  • Carbohydrate Antigen (CA) 125
  • CA 15-3
  • CA 19-9
  • Estrogen or Progesterone receptors (ER/PR)
  • Human Chorionic Gonadotropin (hCG)
  • HER2 (neu) or neu
  • (Prostate Specific Antigen) PSA
  • Parathyroid hormone (PTH) and Ca++
  • Thyroglobulin (TG)
• Alpha-fetoprotein (AFP)


  Tumor marker for nonseminomatous testicular germ cell cancer
• Alpha-fetoprotein (AFP)


  • Normal sources are liver and fetal liver/yolk sac
  • Elevated in pregnancy and nonneoplastic liver disease
  • Used for screening in high-risk populations for liver cancer
• β2– microglobulin


  Part of class I MHC molecule, elevated in B-lymphocyte malignancies
• β2– microglobulin


  • Higher levels imply poor prognosis in multiple myeloma
  • Elevated in inflammatory and high cell turnover conditions
• Calcitonin and Serum Calcium (Ca++)


  Tumor marker for familial medullary thyroid carcinoma
• Calcitonin and Serum Calcium (Ca++)


  • In hypercalcemia, increased calcitonin is expected
  • Serum Ca++ may be low when calcitonin is elevated in medullary carcinoma
  • Can be elevated in other forms of cancer
• CD markers


  Associated with specific WBC malignancies
• CD markers


  • Indicate WBC increase such as infection
• Carcinoembryonic antigen (CEA)


  Tumor marker for colorectal, breast, and lung cancer
• Carcinoembryonic antigen (CEA)


  • Normal sources are tissues of endodermal origin
  • Elevated in renal failure, nonneoplastic liver and intestinal disease, and with age and smoking
• Carbohydrate Antigen (CA) 125


  Tumor marker for ovarian adenocarcinoma
• Carbohydrate Antigen (CA) 125


  • Normal sources are ovaries and various other tissues
  • Elevated in endometriosis, pelvic inflammatory disease, uterine fibroids, and pregnancy
  • Screening is only recommended for women with a family history of ovarian cancer
• CA 15-3


  Tumor marker for breast cancer, also elevated in other cancers
• CA 15-3


  • Normal source is mammary tissue
  • Elevated in benign breast and liver disease
• CA 19-9


  Tumor marker for pancreatic cancer
• CA 19-9


  • Normal source is sialylated Lewis^a blood group antigen
  • Elevated in benign hepatobiliary and pancreatic conditions, and some nonpancreatic malignancies
  • Subjects who are Lewis a and b negative cannot synthesize CA 19-9