Immune Defects in Cancer

The host immune system is one of the most important elements of antitumor defense. The idea of cancer immunosurveillance proposed by Sir Macfarlaine Burnet and Lewis Thomas (1,2) has been recently highlighted in experiments with gene knockout mice. Compared with wild-type mice, mice lacking sensitivity to either interferon-γ (IFN-γ receptor-deficient mice) or all interferon (IFN) family members (i.e., Stat 1 -deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene (3). Mice lacking lymphocytes and IFN-γ (RAG2-/- x STAT1-/- mice) also had an increased incidence of spontaneous mammary tumors (4). The development of tumors and metastatic disease in nonimmunocompromised hosts can be considered as a result of an inadequate immune response against tumors and the evasion of tumor cells from the host immune system (5). The correlation between the presence of tumor-infiltrating lymphocytes and survival of patients with melanoma (6), breast (7), bladder (8), colon (9), neuroblastoma (10), ovary (11), and prostate (12) cancers gives hope that the manipulation of tumor escape mechanisms, by immuntherapeutic interventions, may provide clinical benefits. In tumorbearing animals and cancer patients, however, the immune response against tumors is markedly depressed. The fact that the resection of progressively growing solid tumors restores protective antitumor immunity in experimental models of cancer (13) demonstrates the ability of the immune system to defend against an established tumor.