Tumor and Transplant Immunology

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Practical Urology: EssEntial PrinciPlEs and PracticE

T-lymphocytes as mediators in the stimulation

antibody-dependent cell-mediated cytotoxicity

or suppression of the immune system to attack

(ADCC). ADCC also accelerates T-cell activity.

cancer or prevent organ rejection.

The digested foreign cell proteins are presented

on the major histocompatibility complex (MHC)

Antibodies

molecules of the antigen-presenting cell (APC)

as peptides.

Antibodies have assisted with the detection,

Antibodies are proteins made by B cells in

prognosis, and treatment of urologic cancers.

response to a foreign antigen. Each antibody

Oncofetal antigens such as AFP and b-hCG have

binds to a specific antigen. The more specific the

been identified as important markers in germ

antibody, the greater the strength of the anti-

cell tumors.Several growth factor receptors have

body–antigen bond.6 All antibodies are com-

also been associated with tumors and have

posed of light and heavy polypeptide chains. The

become important prognostic factors as well as

number of chains may vary, but usually there are

potential therapeutic targets. Prostate cancer

two of each type. Every heavy chain is paralleled

has received the most notoriety in the develop-

by a light chain.6 Fc receptors on the heavy chain

ment of antibodies to PSA. Other antibodies

regions which allow for antibody function.

being tested for prostate cancer include pros-

Antibodies function in two distinct manners.

tatic acid phosphatase and prostate-specific

They either directly attack the antigen or they

membrane antigen. B-hCG and CEA are

activate the complement system. Direct attack

expressed on some transitional cell carcinomas,

initiates agglutination, precipitation, neutraliza-

although this tends to be a minority of these

tion, or lysis. Agglutination involves binding

cancers. Germ cell tumors appear to have the

multiple large particles with antigens on their

largest potential for therapeutic intervention in

surfaces. The antigen–antibody bonding can

that b-hCG and AFP are commonly used to

also create a molecular complex so large that it

detect and prognose outcome with regard to

is rendered insoluble and precipitates. Neu-

cancer. The relative levels of each of these tumor

tralization occurs when the antibodies envelope

markers enable classification of the tumors with

the antigen. Lysis occurs when specific and

regard to risk and survival. Monoclonal anti-

potent antibodies directly attack the cell mem-

body immunotherapy has met with limited suc-

branes and rupture the cell.

cess. In some cases, tumor cell death has been

The direct attack of antibodies on antigens is

accomplished; however, only with unacceptable

not usually completely sufficient. Antibodies

side effect risk profiles. Limited or incomplete

compound their effect by activating the cascade

tumor cell killing therapies have also been uti-

of the complement system consisting of approx-

lized with moderate success. Most of these ther-

imately 20 different proteins.6 These proteins

apies remain investigational at this point.

are usually inactive enzyme precursors that are

activated by the antigen–antibody complex.

Cytotoxic and T-helper Cells

When an antibody binds with an antigen, a spe-

cific reactive site on the antibody is activated.

This reactive site initiates a cascade of reactions

T-cells are either cytotoxic (CD8+) or helpers

within the complement system. A single anti-

(CD4+). Unlike antibodies, which react to intact

body–antigen combination activates many mol-

proteins only, the cytotoxic T-cells react to pep-

ecules of the complement system and increasing

tide antigens expressed on the surface of a cell.

amounts of enzymes. The multiple end products

Peptide antigens are proteins that have been

formed help prevent damage by the offending

digested and presented as peptides displayed on

agents.

the MHC. The peptide and the MHC together

Importantly, the complement system in turn

attract T-cells. Cytotoxic T-cells are specific for

initiates opsonization and phagocytosis.A prod-

class I MHC molecules, while T helper cells are

uct of the complement cascade strongly activates

specific for class II MHC molecules.

phagocytosis by neutrophils and macrophages.

After attaching to the MHC-peptide complex

The neutrophils and macrophages dock onto

expressed on a cell,the cytotoxic T-cell destroys the

the Fc receptor and literally digest the bound

cell by enzymatically perforating the membrane

cell. This type of antibody-mediated process is

or by apoptosis. The cytotoxic T-cell will continue