Cancer = Neoplasia

Abnormal new growth due to excessive increase in number of cells (continuous proliferation). This increase is progressive

)non reversible ,(non physiologic , purposeless.

Basic Facts:Neoplasia arises only in cells able to proliferate.Neoplasia cells do not differentiate.Hyperplasia often pretend neoplasia.

Some solid cell tumors may proliferate more slowly than normal cells.

Cancer usually follows extracellular stimulus (chemical, physical or biological).

Basic Facts:

Cancer cells may be dormant for Long time.

Rarely cancer cells may regress spontaneously, but their behavior may be modified with hormones, immunity or chemotherapy.

Cancer are usually multicentric

• Activated oncogenes transform normal cells into cancerous cells.

• Transformed cells have increased growth, loss of contact inhibition, tumor specific transplant and T antigens.

• The genetic material of oncogenic viruses becomes integrated into the host cell's DNA.

Cancer

• Oncogenic DNA Viruses

– Adenoviridae

– Herpesviridae

– Poxviridae

– Papovaviridae

– Hepadnaviridae

Oncogenic Viruses

Oncogenic RNA virusesRetroviridae

Viral RNA is transcribed to DNA which can integrate into host DNAHTLV 1HTLV 2

Tumors are two types

Benign or simple tumor .

Malignant tumor or cancer

Benign (simple)

Malignant (cancer)

Cells are usually differentiated, mature and resemble cells of the tissue

Cells are atypically undifferentiated and malignant.

Benign (simple)

Malignant (cancer)

Grow slowly in

all directions but is surrounded by fibrous capsule and so does not invade the surrounding tissue.

Grow rapidly invading the surrounding tissue and is not surrounded by any capsule.

Benign (simple)

Malignant (cancer)

Never spread to other parts of the body.

NO Metastasis

May be fragmented and carried in blood or lymph vessels to other parts of the body.

Metastasis

Carcinoma Sarcoma

Epithelial origin

Lining or glandular

Mesenchymal originConnective tissue,

Blood cells Muscles

Evidence for immune reactivity to tumors

• Tumors that have severe lympho-reticular infiltration have a better prognosis than those that do not. 

• Certain tumors regress spontaneously (e.g., melanomas, neuroblastomas). 

• There is an increased incidence of primary and secondary malignancies (particularly lympho-reticular tumors) in immunodeficient patients. 

Evidence for immune reactivity to tumors • Antibodies and immune T lymphocytes

(in cytotoxicity and mitogenic response assays) have been detected in patients with tumors. 

• The young and the very old have an increased occurrence of tumors. These members of the population often have an immune system that is less effective.

• Finally, animals can be specifically immunized against various types of tumors.

Tumor associated antigens

• Neo-antigens

• Onco-fetal antigens

• Tumor associated transplantation antigens (TATA) = Tumor rejection.

Onco-fetal antigens• Onco-fetal antigens may

appear due to de-repression of  genes that were only expressed early in life.

• Alpha-fetoprotein (AFP)

• Carcino-embryonic antigen (CEA ).

Alpha-fetoprotein (AFP)• The normal range of AFP

concentrations in humans is 0-20 ng/ml.

• A 5-fold or higher rise in:

• A) Hepatomas

• B) Non-seminal testicular carcinoma.

Carcino-embryonic antigen (CEA ).

• CEA levels in normal people range up to 2.5 ng/ml.

• Increase significantly in:

• Colorectal cancers

Tumor associated transplantation antigens (TATA) on viral tumors=

Oncogenic viruses

• Hepatitis-B virus in hepatic carcinoma

• Papilloma virus in cervical cancer

Table 1. Immunotherapy of tumors

Active

Non-specificBCG, Propionibacterium acnes,

levamisole, cytokine genes, etc.

SpecificKilled tumor cells or their extract,

recombinant antigens, idiotype,

Passive

NonspecificLAK cells, cytokines

SpecificAntibodies alone or coupled to drugs,

pro-drug toxins or radioisotope; bispecific antibodies; T-cells

CombinedLAK cells and bispecific antibody

 * BCG: Bacillus Calmette Geurin is a bovine strain of Mycobacterium tuberculosis

Table 2. Non-specific active immunotherapy: biological response modifiers (BRMs)

Type of BRMExamplesMajor effect

Bacterial product

BCG, P. acnes, muramyl di-peptide, trehalose dimycolate

Activate macrophages and NK cells (via cytokines(

Synthetic molecules

Pyran, poly I:C, pyrimidines

Induce interferon production

CytokinesInterferon- αβγ IL-2, TNF

Activate macrophages and NK cells

Table 3. Cytokine therapy of tumors

CytokineTumor type and resultAnti-tumor echanism(s)

IFN- α, β

remission of hairy cell leukemia, weak effect on some carcinomas

increased expression of class I MHC, possible cytostatic anti-tumor effect,

IFN-γ

remission of peritoneal carcinoma of ovary: ineffective systemically

increased MHC antigens; macrophage, Tc and NK cell activation

IL-2remission in renal 

carcinoma and melanoma

T-cell proliferation and activation, NK cells activation

TNF- αcan reduce malignant 

ascitesmacrophage and 

lymphocyte activation

• Monoclonal anti-tumor antibodies have been used in different forms for the treatment of cancer, either because of their direct effect or as vehicles to target anti-cancer drugs, toxins and the non-specific components of the host's immune system to the site of tumor