Introduction

In most tissues of a mature organism, a balance is maintained between cell renewal and cell death. Occasionally, though, cells arise that no longer respond to normal growth-control mechanisms. These cells give rise to clones of cells that can expand to a considerable size, producing a tumour, or neoplasm.

Benign, if it is not capable of indefinite growth and the host survives.

Malignant, if the tumor continues to grow indefinitely and spreads (metastasizes), eventually killing the host. This uncontrolled growth may be due to up regulation of oncogenes (cancer-inducing genes) and/or down regulation of tumor suppressor genes (that normally inhibit tumor growth often by inducing cell death).

Evidence For Immune Reactivity To Tumors

There is a lot of evidence that tumors can elicit an immune response. Such evidence includes:

• · Tumors that have severe mononuclear cell infiltration have a better prognosis than those that lack it.
• · Certain tumors regress spontaneously (e.g., melanomas, neuroblastomas), suggesting an immunological response.
• · Some tumor metastases regress after removal of primary tumor which reduces the tumor load, thereby inducing the immune system to kill the residual tumor.
• · Although chemotherapy leads to rejection of a large number of tumor cells, the few tumor cells that evade the action of the drugs can outgrow and kill the host. However, the immune system may be able to mount an attack against the few tumor cells that are spared by the chemotherapeutic agent.
• · There is an increased incidence of malignancies in immuno-deficient patients such as AIDS patients who are susceptible to Kaposi sarcoma and transplant patients who are susceptible to Epstein Barr virus (EBV)-induced lymphoma.
• · Tumor-specific antibodies and T lymphocytes (detected in cytotoxicity and proliferative response assays) have been observed in patients with tumors.
• · The young and the old population have an increased incidence of tumors. These members of the population often have an immune system that is compromised.
• · Hosts can be specifically immunized against various types of tumors demonstrating tumor antogens can elicit an immune response.

TUMOR ASSOCIATED ANTIGENS

There are 2 main types of tumor antigens:

Tumor-specific transplantation antigens (TSTA) which are unique to tumor cells and not expressed on normal cells. They are responsible for rejection of the tumor.

Tumor associated transplantation antigens (TATA)

The majority of tumor antigens are also present on normal cells and are referred to as tumor associated transplantation antigens. They may be expressed at higher levels on tumor cells when compared to normal cells. Alternatively, they may be expressed only during development of cells and lost during adult life but re-expressed in tumors.

Tumor-associated developmental antigens or onco-fetal antigens

These include alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) found secreted in the serum. AFP is found in patients with hepatocellular carcinoma whereas CEA is found in colon cancer. These are important in diagnosis.AFP is produced only as a secreted protein whereas CEA is found both on cell membranes and in secreted fluids. Since secreted antigens contribute little toward immunity against tumors, the role of these neo-antigens in immuno-surveillance is questionable.

TUMOR ASSOCIATED TRANSPLANTATION ANTIGENS ON VIRAL TUMORS

Viruses that cause human tumors include:

• DNA viruses
• Papova (papilloma, polyoma) viruses: Papilloma virus causes cervical cancer.
• Hepatitis virus: Hepatitis B virus causes hepatocellular cancer.
• Adenoviruses may also be tumorigenic.
• RNA viruses
• Retroviruses

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