Tumor Markers and Cancer Biology Quiz

Immunology & Serology I - 0202308

• Course offered by Al-Quds University, Faculty of Health Professions, Department of Medical Laboratory Sciences
• Instructor: Dr. Rasmi Abu-Helu (Ph.D., Immunology)
• Course code: 0202308

Tumor Immunology

• Course covers tumor biology, tumor antigens, clinically relevant tumor markers, laboratory tests for tumors, immune defenses against tumors, immunoediting and tumor escape, and immunotherapy.

Chapter Overview

• Topics covered are tumor biology, tumor antigens, clinically relevant tumor markers, laboratory tests for tumors, immune defenses against tumors, immunoediting and tumor escape, and immunotherapy.

Learning Objectives

• Students will be able to compare benign and malignant tumors.
• Students will be able to define and give examples of proto-oncogenes.
• Students will be able to describe the role of oncogenes.
• Students will be able to describe the characteristics of the major body defenses against cancer.
• Students will be able to identify and discuss the characteristics of tumor markers.
• Students will be able to discuss new developments in cancer diagnostic testing.

Introduction to Tumor Biology

• Tumor (neoplasm) is an abnormal cell mass.
• Cancer is malignant tumors that can spread.
• Cancer is caused by mutations in proto-oncogenes and tumor suppressor genes.
• Causes include uncontrolled cell division and other characteristics

Definitions

• Neoplasm: An abnormal mass of tissue resulting from uncontrolled growth of normal cells, even after the growth stimulus is removed.
• Benign tumor: A mild and non-progressive tumor that pushes aside normal tissue but does not invade it as it expands.
• Malignant tumor: Consisting of poorly differentiated cells that grow rapidly, invade surrounding tissue, and rob normal tissue of nutrients.
• Metastatic tumor: A secondary tumor derived from a malignant primary tumor.

Characteristics of Cancer Cells

• 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 the presence of inflammation.

Tumor-Associated Antigens

• For immune system to react against tumor, it must have antigens recognized as foreign.
• Examples include enzymes, receptors, and membrane antigens, etc.
• Most relevant are surface membrane molecules, which can be either antigenic or suppress membrane proteins essential for immune recognition and activation.

Tumor-Specific Peptides

• Intracellular proteins expressed on tumor cells with MHC class I and II.
• This expression can be chemically induced.

Virus-Induced Tumors

• Tumors caused by viruses.
• Tumor cells express viral antigens on their surfaces.
• Tumor cells recognized as non-self by the immune system.

Genome-Encoded Tumor Antigens

• Oncogenes: if downregulated, the protein product can lead to tumor.
• Proto-oncogenes: found in all nucleated cells (yeast to human), involved in cell growth; alterations in gene expression or protein structure may lead to abnormal cell growth.

Oncofetal Antigens

• Found on normal fetal cells.
• Produced in minute amounts after birth.
• Become expressed later after malignant transformation.
• Examples: a-fetoprotein (AFP) and carcinoembryonic antigen (CEA).
• ~90% of colorectal cancers have CEA.

Immunity to Tumors

• Natural immunity:
  • Macrophage-mediated cytotoxicity: Macrophages killing tumor cells on contact.
  • NK cells: 50% of tumors have mutations decreasing MHC class I on their surfaces, facilitating killing by NK cells.
• Humoral-mediated immunity:
  • Antibodies: Antibodies produced targeting tumor cell surface antigens.
  • Lysis of tumor cells (via complement activation and antibody-dependent cellular cytotoxicity (ADCC) reactions involving NK cells, PMNs, and macrophages).
• T cell-mediated immunity:
  • Cytokines: IL-1 activates T, B, and NK cells, TNFα destroys tumor cells, IFNg produced by activated T, B, and NK cells.
  • CTLs (cytotoxic T lymphocytes): directly lyse tumor cells.

Immune Defenses Against Tumor Cells

• Immune system comprises various components (e.g., NK cells, macrophages, CTLs, antibodies, cytokines) acting in concert to eliminate or control tumor cells.
• Elimination, equilibrium, and escape phases are associated with immune response to tumors.
• These processes involve apoptosis and other mechanisms to eliminate altered cells and maintain immune surveillance to control tumor growth.

Body Defenses Against Cancer

• Various factors contribute to immune evasion by tumors including antigen loss variants of tumor cells, defective MHC I expression or dysfunction and immunosuppressive cytokines that prevent effective anti-tumor immune response.

Immunoediting and Tumor Escape

• Elimination phase: robust innate and adaptive immune responses kill tumor cells
• Equilibrium phase: immune system controls limited number of altered cells
• Escape phase: immune system is suppressed, and inflammation promotes uncontrolled tumor growth.
• Tumor cells highly altered & more resistant to immune responses; apoptosis is impaired.

Tumor Evasion of Immune System

• Anti-tumor antibodies might block sites for CTL binding.
• Tumor cells might express less class I MHC which prevents CTL-mediated death.
• Tumor cells might provide poor costimulatory signals.

Tumor Markers

• Glycoproteins found in small amounts in normal serum, but elevated in certain cancer types.
• Used to screen for cancer, monitor therapeutic response, and determine tumor burden.

Carcinoembryonic Antigen (CEA)

• Used in management of GIT tumors (e.g., colon cancer, adenocarcinoma of the colon, pancreas, liver, lung)
• Found in inflammatory bowel disease (IBD), ulcerative colitis, polyps, tumors of the GIT, Crohn disease, and cigarette smokers.
• Highest levels of CEA are found in metastatic disease.
• Normal CEA levels in normal people are up to 2.5 ng/ml.
• Levels 4-5 times normal have been used to predict colorectal tumor recurrence.

α-Fetoprotein (AFP)

• High levels in patients with hepatocellular carcinoma & hepatoblastoma, testicular & ovarian cancer, viral hepatitis & cirrhosis, and ulcerative colitis.
• Very important marker in monitoring cancer therapy.
• Normal range of AFP concentrations in humans is 0-20 ng/ml.
• A 5-fold or higher rise is used for monitoring hepatomas and testicular cancers.
• AFP levels may also be raised in some non-malignant liver conditions like cirrhosis, hepatitis.

Human Chorionic Gonadotropin (hCG)

• Composed of 2 subunits (α & β, β-hCG).
• Found in serum and urine during pregnancy.
• Produced by neoplastic cells of testicular cancer and other tumors.
• Levels useful for evaluating patients with gestational trophoblastic disease, testicular tumors, and ovarian germ cell tumors.
• Normal range in adults is <15 ng/mL.

Prostate-Specific Antigen (PSA)

• Glycoprotein that dissolves seminal gel after ejaculation.
• Found in very low amounts in blood of normal individuals.
• Increased in prostate cancer, benign prostatic hypertrophy (BPH), acute & chronic prostatitis.
• Levels correlate with prostate size, stage of cancer, response to treatment.
• Used in screening for prostate cancer—used in conjunction with digital rectal examination.
• PSA level below 4 ng/mL.

Clinically Relevant Tumor Markers

• Biological substances found in increased amounts in blood, body fluids, or tissues of patients with specific types of cancers.
• Concentration depends on tumor cell proliferation and size; elevated levels indicate a significant tumor mass.
• Ideal marker is highly sensitive and specific.

Clinical Uses of Tumor Markers

• Population screening: used to identify cancer in asymptomatic people.
• Diagnosis: used to identify cancer in a particular patient.

Common Serum Tumor Markers

• Various tumor markers (e.g., AFP, CA 125, CA 19-9, CEA, hCG, PSA) are associated with specific cancers or conditions, and are used clinically for diagnosis, prognosis, and monitoring.

Laboratory Tests for Tumors

• Immunohistochemistry: uses labeled antibodies to detect tumor antigens in tissue biopsies.
• Immunoassays: measures levels of circulating tumor markers.
• Molecular methods: detects genetic mutations associated with cancer (e.g., PCR, karyotyping, FISH, microarray, DNA sequencing).

Immunotherapy

• Also known as biological response modifier therapy.
• Uses the ability of the immune system to destroy tumor cells.
• Active immunotherapy: stimulates patient's immune system to respond to tumor antigens (cancer vaccines).
• Passive immunotherapy: administration of soluble components of the immune system (e.g., cytokines) and monoclonal antibodies that target specific tumor antigens (e.g., surface antigens, receptors, angiogenesis factors, and immune checkpoint molecules).
• Adoptive immunotherapy: transfer of cells of the immune system (e.g., TILs, CAR-T cells) to patients.

Test your knowledge on tumor markers such as β-HCG, PSA, and CEA. This quiz covers their roles, normal levels, and associated conditions in cancer biology. Assess your understanding of key concepts related to malignancy and cancer cell characteristics.