Immune mechanisms and tumor dormancy

The natural occurrence of tumor dormancy in man is reviewed based on observations made by a distinguished surgeon and two pathologists after a lifetime of practice. They concluded that dormancy is the result of immune mechanisms preventing the growth of microscopic metastases already present following curative surgery. Six cases of non-small-cell lung cancer are described in patients randomized to receive specific active immunotherapy in controlled clinical trials. Three patients had nonregional metastases at 11, 12 and 14 years. Two had regional recurrence after 9 years and in one patient a small hilar-node metastasis was found at necropsy after 7.6 years. In each case an immunodepressive event or drug treatment preceded resurgent growth. Animal models of tumor dormancy are reviewed and the evidence is clear that dormancy may be induced by manipulating immune mechanisms, resulting in cells remaining in mitotic arrest, or tumor cell proliferation is balanced by an equivalent rate of cell death. Based on these observations future clinical strategies should de developed to induce the dormant state in micrometastases in the adjuvant setting.