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[Cancer Research 61, 5132-5136, July 1, 2001]
© 2001 American Association for Cancer Research

Immunology

Proliferative Activity of Intratumoral CD8+ T-Lymphocytes As a Prognostic Factor in Human Renal Cell Carcinoma

Clinicopathologic Demonstration of Antitumor Immunity1

Osamu Nakano, Makoto Sato, Yoshitaka Naito, Kenichi Suzuki, Seiichi Orikasa, Masataka Aizawa, Yasuyoshi Suzuki, Ichirou Shintaku, Hiroshi Nagura and Haruo Ohtani2

Departments of Pathology [O. N., Y. N., H. N., H. O.] and Urology [O. N., M. S., K. S., S. O.], Tohoku University Graduate School of Medical Science, Sendai 980-8575; Department of Urology, Ishinomaki Red-Cross Hospital, Ishinomaki 986-0015 [M. A.]; and Department of Urology, Sendai Social Insurance Hospital, Sendai 981-0912 [Y. S., I. S.], Japan

Tumor-infiltrating lymphocytes, particularly CD8+ T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8+ but also CD4+ T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8+ T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8+ T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.




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