It is well documented that metastatic recurrence is a frequent cause of cancer development even many years after removal of primary tumor [
6]. It is also well known that immunosuppressive therapy in post-transplantation patients frequently induces various
de novo cancers [
12]. We believe that in our case tumor dormancy of residual malignant cells that lasted for 8 years, had been interrupted after the changes in the patient's immune status immediately following kidney transplantation and immunosuppressive regime. Persistence of circulating tumor cells may represent residual disease and is known to be associated with a higher risk of recurrence; however, the status of tumors during the period of dormancy is poorly understood. Various factors have been identified as possible contributors to tumor dormancy and subsequent recurrence, including tumor angiogenesis, cell proliferation and cell cycle arrest, cancer cell interactions with the microenvironment, and changes in immune status [
18]. Various published results have described that oncogene inactivation can induce tumor regression and that oncogene reactivation leads to rapid tumor formation. There are reports demonstrating that at least in some cases tumor dormancy can be interrupted by a transient change in the microenvironment due to local inflammation. Animal studies also indicate the importance of T-cell immunity in the induction and maintenance of tumor dormancy. Dormant micrometastases may be triggered to expand when host or cancer cell factors change to promote progressive metastatic growth. In our case the immunosupression was a probable trigger of such expansion. Tumor dormancy represents an existence of an apparent balance between tumor cell elimination and proliferation, or between effective immune surveillance and immune escape. According to the theory of immunosurveillance, originally proposed by Burnet and Thomas in 1957, the immune system protects the host against tumor development by recognizing and eliminating transformed cells, therefore, the dysfunction of the immune system leads to increased risk of cancer incidence. Published data obtained from more recent mouse models and from human clinical trials supports this theory and suggests the existence of a more complex picture of immunosurveillance, which includes an active role of the immune system also in facilitating immunoselection of malignant cells and the emergence of tumor escape variants with low immunogenicity. New data indicate that the immune system can facilitate tumor progression, at least in part, by sculpturing the immunogenic phenotypes of tumors as they develop [
19]. It has been confirmed in animal studies that tumors developing in immunodeficient mouse strains tend to be more immunogenic, while tumor cells arising in the presence of a fully functional immune system are less immunogenic. Thus, in the case of a functional immune system highly immunogenic tumor cells that are recognized by the immune system are eliminated while tumor variants that have better survival features, such as low immunogenicity, are selected. This selective pressure leads to the expansion of a new population of cells with multiple defects capable of evading immune response. These residual tumor cells may be circulating in patients in long remissions and they may represent a different stage of tumor control mechanisms, called an immunological equilibrium. Some of the immune escape mechanisms, notably downregulation of MHC class I molecules that are necessary for antigen presentation of tumor specific peptides to cytotoxic T-lymphocytes, are most pronounced in metastatic lesions, as it has been demonstrated in RCC [
20]. This suggests that the selection pressure is strong in the metastatic stage of cancer development. Thus, the immune system might play a dual role: protecting the host by eliminating strong variants of tumor cells and promoting tumor development by selection of immunologically weak tumor variants that give rise to a new metastatic progression. Therefore, the immune system can maintain a subclinical tumor in an equilibrium state. We propose that a stage of immunological equilibrium between tumor growth and elimination had been reached in our patient after the excision of the malignant kidney. After transplantation, the administration of immunosuppressants changed the immunological equilibrium and probably triggered the pulmonary metastatic malignant growth of dormant tumor cells from the primary renal carcinoma. This supports the importance of immune surveillance as part of tumor-host interaction during cancer progression and the key role of tumor escape in immunosupressed individuals.