tumor immunology

• Tumor (neoplasm)


  An abnormal cell mass
• Tumor


  • Benign or malignant
  • Cancer = malignant tumor that can spread
• Cancer


  Malignant tumor caused by mutations in proto-oncogenes and tumor-suppressor genes, resulting in uncontrolled cell division and other characteristics.

  Proto-oncogenes are normal genes that have a positive influence on cell proliferation and development. Sometimes, mutations in proto-oncogenes can convert them to oncogene-like genes, which have DNA sequences similar to those found in the oncogenes of transforming viruses. Cell division is normally inhibited by the action of tumor suppressor genes. These genes have both “gatekeeper” and “caretaker” functions
• Types of neoplasm


  • Benign neoplasm: slow growth, restricted anatomic location and does not usually cause death
  • Malignant neoplasm: slow or rapid growth, anaplasia, invasion of the body and metastases, can result in death. Also known as CANCER.
• Tumor


  Swelling resulting from anaplasia which is due primarily to an increase in tissue mass
• Evidence for immune response to tumors


  • Spontaneous regression
  • Long term indolence
  • Mononuclear response
  • Post surgical detection of malignant cells
  • Autologous tumors
  • Positive immediate and delayed hypersensitivity skin test
• Characteristics of cancer cellsby Hannah and Weinberg


  • Sustained proliferation
  • Resist death
  • Induce angiogenesis
  • Immortality
  • Invasion and metastasis
  • Avoid suppressors of cell growth
  • Altered metabolism
  • Evasion of immune defenses
  • Genomic instability
  • Accelerated growth in presence of inflammation
• Tumor-specific antigens (TSAs)


  • Oncofetal antigens
  • Viral component proteins or enzymes
• Oncofetal antigen


  Present during normal fetal development, lost during differentiation of tissue and reappear during malignancy. When becoming adult is should be loss.
• Alpha-fetoprotein (AFP)


  Synthesized and secreted in the liver, found in the cord blood, detected in hepatomas, also seen in non-malignant cases (cirrhosis/hepatitis), used as a prognostic index or marker of chemotherapeutic success
• Tumor-specific antigens (TSAs)


  Unique to the tumor, coded by mutated proto-oncogenes or tumor-suppressor genes, examples include BCR/ABL gene rearrangement in CML and antigens coded for by cancer-causing viruses
• Tumor-associated antigens (TAAs)


  • Expressed in tumor cells and normal cells
  • Shared tumor-specific antigens
  • Differentiation antigens
  • Overexpressed antigens
• Carcinoembryonic antigen (CEA)


  Detected in the gut, liver & pancreas of normal fetus during 2nd trimester of pregnancy, low levels in adult serum, elevated in 70% of colon cancer cases and also in non-malignant cases (e.g. cigarette smoking), used as a prognostic marker
• Clinically relevant tumor markers


  Biologic substances found in increased amounts in blood, body fluids, or tissues of patients with a specific type of cancer, concentration in serum depends on amount of tumor proliferation and tumor size, elevated level indicates significant tumor mass
• Clinical uses of tumor markers


  • Population screening
  • Diagnosis
  • Patient prognosis
  • Monitoring response of cancer patient to therapy
• Common serum tumor markers


  • AFP - Liver, testicular Cancer (S, D, P, M)
  • CA 125- Ovarian Cancer (S, D, P, M)
  • CA 19-9 - Pancreatic Cancer (D, P, M)
  • CEA - Colorectal, breast cancer (P, M)
  • hCG - Testicular, trophoblastic cancer (D, P, M)
  • PSA - Prostate Cancer (S, D, P, M)
• Galactosyltransferase


  Ovarian cancer
• Galactosyltransferase isoenzyme II


  Pancreatic cancer
• Histaminase


  Medullary thyroid cancer
• IgA


  Multiple myeloma
• IGF-I


  Pituitary cancer
• Igs


  Multiple myeloma
• Inhibin


  Granulosa cell tumor
• Insulin like growth factor


  Non-islet cell tumor
• Katakalcin


  Medullary thyroid cell cancer
• 17-Ketosteroids


  Adrenal/pituitary cancer
• LASA-P


  Various carcinoma, Hodgkin's L
• Neuron-specific enolase


  small cell lung carcinoma
• Pancreatic polypeptide


  Endocrine tumor
• P 21 protein


  Breast cancer
• POA


  Pancreatic cancer
• PSA


  Prostrate cancer
• PS-2 protein


  Breast cancer
• TdT


  Acute lymphocytic leukemia
• Thyroglobulin


  Thyroid cancer
• TPA


  non specific
• TAG 72


  Gastric carcinoma
• Urokinase inhibitor


  Bladder tumors
• Immunohistochemistry


  • Uses labeled antibodies to detect tumor antigens in tissue biopsies
  • used as an effective technique of classifying tumors of uncertain origin because many tumors can have a similar appearance histologically
• Immunoassays


  • Measure levels of circulating tumor markers
  • A third factor that can affect immunoassay results is antigen excess.
  • When the measurements exceed the linear range of reportable results, this phenomenon is called the high-dose hook effect. this effect can result to falsely decreased measurement in the antigen excess area.