Recruitment of MHC-Restricted Cytotoxic T Lymphocytes Specific for Renal Cell Carcinoma to the Tumor In Situ

Analysis of the anti-tumor responses of patients with melanoma serves as a model for studies of other solid tumors. The identification of specific cytotoxic T lymphocytes has led to the development of new strategies for treatment of metastatic melanoma, including various immunotherapies. Although the cellular and molecular basis of these reactions requires further characterization, several observations indicate that host anti-tumor responses develop against some renal cell carcinoma (RCC) cells. Many primary and metastatic lesions display rich lymphocytic infiltrates and metastatic lesions spontanously disappear in about 0.5% of patients. Furthermore systemic application of cytokines, such as interleukin-2 (IL-2) and IFN-alpha, or adoptive transfer of lymphokine activated killer (LAK) cells and tumor infiltrating lymphocytes (TIL) have led to partial or complete remission of metastatic disease in some cases (1). The predominant cells that have been cultivated from TIL populations of most solid tumors are nonspecific effector cells such as natural killer (NK) or LAK cells; such cells can induce a certain degree of tumor regression when adoptively transferred together with high doses of IL-2 (2,3). In contrast, tumor infiltrating cytotoxic lymphocytes (CTL) displaying specificity for a given tumor have been shown to be 50–100 times more effective in reducing tumors in an animal model (4). Similarly specific immune recognition of some melanoma tumors was clearly established through the identification of CD8-positive, MHC-restricted CTL that effectively lysed autologous tumor cells in vitro (5). The prevalence of such cells in patients remaining in remission suggested that these cells are responsible for inhibiting further metastasis.