Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers.

2. Immunity and immune system
TUMOR IMMUNOLOGY
by: Dr
Mohamed. M. Amin
Associate professor of microbiology and immunology
Faculty of medicine - Aswan University
Egypt

3. • Immuno-surveillance: is the ability of the
immune system to prevent the development of
most tumors through early recognition and
destruction of tumour cells. For this to operate,
tumour cells must develop surface membrane
molecules which might be antigenically new
(tumour antigens) and can be recognized by the
immune system.

4. • Cell proliferation is regulated by:
– Proto-oncogenes:
• These genes are found in normal cells.
• They encode proteins that induce cell proliferation.
• Conversion of proto-oncogenes to oncogens may lead to malignant
transformation of the cell leading to cancer.
– Tumor suppressor genes:
• These genes are also present in normal cells and function to inhibit cell
proliferation e.g. P53 tumor suppressor gene
• Inactivation of tumor suppressor genes leads to excessive cell proliferation.
• Cell death is regulated by:Regulation of apoptosis that occur as a physiological
phenomenon e.g. during aging or as a pathological process
• Imbalance between cell proliferation and cell death occurs due to mutation in genes
regulating one or both of these 2 processes.

5. • Criteria of transformed cells:
• Increased growth rate.
• Alteration in morphological, metabolic and genetic properties of the
cell.
• They can divide indefinitely in serial culture.
• Loss of the property of contact inhibition.
• Reduced serum requirement for growth.
• Appearance of new antigens on the cells.
• They produce tumors when injected in appropriate animals.

6. • Two groups of tumor antigens have been
described:
• Tumor-associated antigens (TAAs) are
antigens that are relatively restricted to
tumor cells but may also be present on
normal tissue
• Tumor-specific antigens (TSAs) are
antigens that are expressed on tumor cells
but not on normal cells
Tumor antigens

7. Tumor antigens
• 1. tumor associated antigens
– Normal cellular proteins that are overexpressed in tumor cells e.g. Human breast
cancer over-express of oncogene-encoded Her-2Neu protein, while normal adult
cells express small amount of this Ag.
– Products of normal genes normally expressed only during embryogenesis and lost
during adult life but re-expressed in tumors so recognized as foreign: Oncofoetal
Ags.
• Alpha fetoprotein (AFP):
– Normal detection in fetal & maternal serum.
– Absent in normal individuals.
– Detected pathologically in hepatocellular carcinoma
• Carcinoembryonic Ag (CEE):
– Detected in GIT cancers specially colo-rectal carcinoma
– Products of mutated oncogenes. HCG in choriocarcinoma

8. 2. Tumor Specific Ag (Mutant cellular gene products):
– They are unique to tumor cells and not expressed on normal cells.
– They are responsible for immunity against the tumor.
• Viral gene products: encoded by genomes of oncogenic
viruses
– Either DNA (Papilloma, HBV) or RNA (Retroviruses
viruses (HTLV-I and HTLV-II)
– chemically or physically induced tumor antigens

9. 3. Over expressed and abnormally expressed cellular
proteins: E.g.
• Melanoma antigen genes (MAGE) these antigens
are normally silent in all tissues except human testis.
• This family of genes are expressed on the surface of
large number of tumors e.g. melanomas, bladder
cancer, breast cancer, skin cancer and prostatic
cancer.

10. Effector Mechanisms Involved in Tumour Immunology
• All components of the immune system can affect the growth and progression of a tumour through
different mechanisms:
I. T Cells:
• These are the main cells responsible for anti-tumour immunity:
• Cytotoxic T cells recognize antigens in association with class I MHC molecules on tumour cells and
kill them. These cells are thought to play the most important role in recognition of tumour cells and
their destruction.
• Helper T cells are activated by shed tumour antigens which become internalized and presented on
the surface of APC in association with MHCII. They secrete cytokines which activate Tc cells,
macrophages, NK cells and B cells. Th cells also produce TNF which is directly toxic to tumour cells.
II. B Cells:
• B cells (as APCs) may play an important role in processing and presenting tumour antigens to Th
cells.
• They produce tumour-specific antibodies, which may cause tumour cell lysis by:
– Fixing complement to the tumour cell membrane, resulting in the formation of membrane attack complex and
consequent lysis of tumour cells.
– Antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells and possibly other cells such as
macrophages.

11. III- Natural Killer Cells
• The activity of NK cells is enhanced by IL-2 and
INF-Ɣ produced by Th1 cells.
• NK cells recognize tumour cells and kill them, loss
of MHCI make the tumor cell as a target for NK cells
• NK cells also kill tumour cells by ADCC.
IV- Monocytes/Macrophages
• Monocytes/macrophages play an important role
through:
– Antigen presentation and cytokine secretion.
– ADCC.
– Direct cytotoxicity of the tumour cells by releasing
TNF, nitric oxide and hydrogen peroxide.

12. Evasion of Immune Response by Tumor:
1-  or absence of MHC-I expression.
2- Stop expression of tumor Ag in rapidly growing tumors.
3- Lack of costimulatory signals (B7, MHC-II,) for T cell activation.
4- Tumor produce immunosuppressive factor (TGF-, Fas-L).
5- Blocking Ab (non complement fixing Ab, so prevent T cell recognition).
6- Soluble Ags shed by tumour.
7-decreased Immune suppression of the host show high incidence of malignancy
8- antigen on the surface masked by sialic acid mucopolysaccharide .

13. Cancer Immunotherapy
1- Specific active immunization:
• Killed tumour cells vaccines + BCG as adjuvants e.g. leukemia
• antiviral vaccines (ex. HBV) decrease incidence of hepatocellular
carcinoma
• Dendritic cell vaccine: DCs derived from patient and incubated with
tumour ag then re infused to the patient
• DNA vaccine IM injection of tumor gene, will be expressed by muscle cells
• Cytokine gene therapy transfection of tumor cell with cytokine gene (IL2
and INF gama) will enhance T cell activation
2- Specific passive immunization:
• Monoclonal antibodies against tumour Ag + cytotoxic drug or toxin or TNF
(magic bullet) (ex. Anti CD20 in B cell lymphoma).

14. 3- Non-specific immunization:
- BCG vaccine  stimulates CMI.in bladder cancer
- Cytokines: IL-2, IFN.
4- Adoptive cellular immunotherapy:
• TIL (Tumour Infiltrating Lymphocyte): Lymphocytes removed from biopsied tumor
and then stimulated in the presence of tumour Ag and cytokines (e.g. IL-2)  in
no. of TIL  re-infused.