1. HOST DEFENCE AGAINST TUMORS:
TUMOR ANTIGENS
These are of two types:
1-Tumor specific antigens (TSAs). These are present on tumor cells only. They are readily demonstrated in chemically induced tumors of rodents as well as some human tumors. TSAs are composed of tumor derived peptides that are presented on the cell surface by MHC class I molecules and recognized by CD8+ (cytotoxic) T cells. Some TSAs are derived from mutant forms of normal cellular proteins. Peptides generated from the mutant proteins when presented on the cell surface by class I MHC molecules, are recognized as non-self by cytotoxic T cells .

4. 2-Tumor associated antigens
2-Tumor associated antigens. These can be found on tumor cells and on some normal cells. They are of 3 categories:
a-Tumor associated carbohydrate antigens representing abnormally glycosylated forms of several different glycoproteins.
b-Differentiation specific antigens that are expressed in specific state of differentiation at which the tumor cell is arrested e.g., CD10, an antigen expressed in early B-lymphocytes and found in many lymphomas and B-cell leukaemias.

5. c-Oncofetal antigens whose expression is derepressed in tumor cells e
c-Oncofetal antigens whose expression is derepressed in tumor cells e.g., alpha-fetoprotein (seen in hepatocellular carcinoma and embryonal carcinoma), and carcino-embryonic antigen (CEA).
These antigens are not targets of host immune response, but their detection is of value in the diagnosis of some tumors. However, they can be targeted by immunotherapy.

6. ANTI-TUMOR EFFECTOR MECHANISMS
Both cell mediated and humoral immunity can have anti-tumor activity.
Cytotoxic T lymphocytes.
Sensitized cytotoxic T-cells play a protective role against virus associated cancers (e.g., EBV-induced Burkitt’s NHL and HPV-induced cervical cancers). Many tumor infiltrating lymphocytes are HLA-restricted cytotoxic T cells directed against T-cell defined tumor antigens. Their use in immunotherapy (harvested, expanded in vitro and reinfused into autologous host) has met some success, as well as transfection of cytokine genes into tumor infiltrating lymphocytes to potentiate their anti tumor effects. Heavy lymphocytic infiltration correlate with good prognosis in some tumors.

7. Natural killer cells (NK)
These are capable of destroying tumor cells without prior sensitization. After activation with IL-2, NK cells can lyse a wide range of tumors especially those with reduced levels of class I MHC molecules (because these engage inhibitory receptors of NK cells). Thus, class I deficient tumors cells that can escape T cell recognition may succumb to NK-cells. NK cells can also participate in antibody dependent cytotoxicity.
Their in vitro expansion and activation to be used in immuno-therapy has met limited success.

8. Macrophages
Gamma interferon (T cell and NK-cell derived) can activate selective macrophage cytotoxicity against tumor cells. These may kill tumor cells by mechanisms similar to microbes (e.g., production of reactive oxygen metabolites) or by production of tumor necrosis factor-alpha.
Humoral mechanisms.
Complement mediated tumor cell lysis and antibody dependent NK cell cytotoxicity.

10. IMMUNE SURVEILLANCE
Putative evidences for anti-tumor immune surveillance
. Increased frequency of cancers in patients with congenital or acquired immunodeficicy (Drug induced, AIDS).
. Increased susceptibility to EBV infections and EBV-associated lymphoma in boys with X-linked immunodeficiency.

11. Tumors may escape immune surveillance by
1-Selection of antigen-negative variants.
2-Loss or reduced expression of histocompatibility antigens, thus becoming less susceptible to cytotoxic T-cell lysis.
3-Tumor induced immunosuppression
Argument against immune surveillance is that tumors developing in immunodeficient patients are mainly lymphomas, which could be the consequence of an abnormal immune system rather than the failure of immune surveillance.