Tumour biology tumor markers & immunology

Tumour biology
A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.

SELF-SUFFICIENCY IN GROWTH SIGNALS

Cell proliferation can be readily resolved into the following steps: The binding of a growth factor to its specific receptor Transient and limited activation of the growth factor receptor, which, in turn, activates several signal-transducing proteins on the inner leaflet of the plasma membrane Transmission of the transduced signal across the cytosol to the nucleus via second messengers or by a cascade of signal transduction molecules Induction and activation of nuclear regulatory factors that initiate DNA transcription Entry and progression of the cell into the cell cycle, ultimately resulting in cell division

SELF-SUFFICIENCY IN GROWTH SIGNALS

GROWTH FACTORS PDGF- chain GROWTH FACTOR RECEPTORS EGF-receptor family PROTEINS INVOLVED IN SIGNAL TRANSDUCTION GTP-binding NUCLEAR-REGULATORY PROTEINS Transcriptional activators CELL CYCLE REGULATORS Cyclins

INSENSITIVITY TO GROWTH INHIBITION AND ESCAPE FROM SENESCENCE: TUMOR SUPPRESSOR GENES

EVASION OF APOPTOSIS

LIMITLESS REPLICATIVE POTENTIAL: TELOMERASE

INVASION AND METASTASIS

Sequence of events in the invasion of epithelial basement membranes by tumor cells

Escape from immune surveillance

Mechanism Tumour not immunosensitive Characterestics No tumour specific antigens

Low expression of MHC factors No antigen processing

Resistance to cell mediated killing Tumour not immunogenic Lack of costimulatory molecules Secretion of immunosuppresive factors Shedding of tumour antigens Induction of T cell tolerance Induction of T cell apoptosis

Escape from immune surveillance

Mechanism Host related Characterestics Growth too fast for immune system Inherited/acquired immunodeficiency Treatment/carcinogen related immunosuppression Deficiency in antigen presentation No access to tumour Expression of immunodominant antigens on parental tumour cells Age

Tumour markers
Tumor markers are indicators of cellular, biochemical, molecular, or genetic alterations by which neoplasia can be recognized

Uses of tumour markers

Be diagnostic and distinguish benign from malignant disease Correlate with the amount of tumor present (socalled tumor burden) Allow subtype classification to more accurately stage patients Be prognostic, either by the presence or absence of the marker or by its concentration Guide choice of therapy and predict response to therapy

Ideal tumour marker

1. The marker is expressed exclusively by the particular tumor 2. Collection of the specimen for the tumor marker assay is easy. 3. The assay itself is reproducible, rapid, and inexpensive

Sensitivity
The ability of the assay to reliably detect the tumour marker in a given biological sample The critical tumour nass that should be present before the marker can be detected The percentage of tumours that express the tumour marker being tested

Specificity
The fidelity with which the assay detects only the tumour marker Presence of other tumours that test positive for the same marker Other non malignant conditions in which the tumour marker is elevated

Tumour markers proteins DNA based RNA Based Epigenetic changes

Immunology

Components

Innate Immunity

Innate immune systemancient immune recognition system of host cells bearing germ lineencoded pattern recognition receptors (PRRs) that recognize pathogens and trigger a variety of mechanisms of pathogen elimination. Cells of the innate immune system include natural killer (NK) cell lymphocytes, monocytes/macrophages, dendritic cells, neutrophils, basophils, eosinophils, tissue mast cells, and epithelial cells

Adaptive Immunity

Adaptive immune systemrecently evolved system of immune responses mediated by T and B lymphocytes. Immune responses by these cells are based on specific antigen recognition by clonotypic receptors that are products of genes that rearrange during development and throughout the life of the organism. Additional cells of the adaptive immune system include various types of antigen-presenting cells

Humoral
Adaptive

Cell mediated

HLA system

HLA ANTIGENS
Class I MHC molecules are expressed on all nucleated cells and platelets class II MHC molecules are mainly expressed on cells that present ingested antigens and respond to T-cell help (macrophages, B lymphocytes, and dendritic cells).

Hypersensitivity reactions