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Clonal Analysis of Lymphocytes from Tumor, Peripheral Blood, and Nontumorous Kidney in Primary Renal Cell Carcinoma¹

Department of Immunology [T-Y. K., K. H., K. I.], General Surgery [M. D. F., C. M. B., K. I.], Urology [A. C. V.], and Clinical Immunology and Biological Therapy [D. R. P.], The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

The immunological properties of lymphocytes from tumor, peripheral blood (PBL), and nontumorous kidney from 16 patients with renal cell carcinoma were characterized at the clonal level with respect to their clonogenic efficiency, phenotypic expression, and cytotoxicity against autologous and allogenic tumor cells. The objectives were to delineate: (a) the quantitative differences in the immunological properties of tumor-infiltrating lymphocytes (TIL) from patient to patient; and (b) the qualitative differences in immunological properties between TIL and lymphocytes from peripheral blood or nontumorous kidney from a single patient. A total of 926 clones were characterized for phenotype expression, and 465 clones were characterized for cytotoxicity. The clonogenic efficiency of TIL varied with individuals: high in one patient; relatively high to moderate in seven patients; low in seven patients, and extremely low in the remaining one patient. The levels of autologous tumor cell lysis by TIL clones also varied with individuals. More than one-third of the TIL clones established in 4 of 13 patients displayed significant (10%) lysis against autologous tumor cells, and in each of the four patients the average percentage of lysis in the total TIL clones was higher than 10%. In two patients, 5 of 26 or 3 of 13 TIL clones were cytotoxic, but averages of percentage of lysis in the total clones were <10%. One 1 or 2 TIL clones of 10–27 total clones were cytotoxic in each of 4 patients, while no cytotoxic TIL clones were found in the remaining 3 patients. Clonogenic efficiency did not correlate with the level of cytotoxicity, and TIL from no tumors displayed both high proliferation and high cytotoxicity at the clonal level. In a majority of patients (12 of 13), most cytotoxic TIL clones against autologous tumor cells also lysed allogenic tumor cells. In contrast, TIL clones lysed only autologous tumor cells in the remaining one patient (patient 2). The clonogenic efficiency of TIL was lower than that of PBL in 6 of 12 patients, while the opposite was true in the remaining 6 patients. The level of cytotoxicity in the PBL clones of these 12 patients primarily correlated with that of the TIL clones. With one exception (patient 2), most cytotoxic PBL clones against autologous tumor cells also lysed allogenic targets in a majority of patients. CD4⁺CD8^- T-cell clones (70–85%) predominated in all patients regardless of the different lymphocyte sources. There was a low but substantial proportion of CD4^-CD8⁺ T-cell clones (15–25%), and the percentages of CD4^-CD8^- clones were very low (<10%). Phenotypic expression of lymphocyte clones, including CD3, CD4, CD8, CD56 (Leu-19), or Leu-7 antigen, did not correlate with their cytotoxic activity. These results suggest that there are: (a) quantitative differences in the immunological properties of the TIL studied here among renal cell carcinoma patients; but (b) no fundamental qualitative differences in immunological properties between TIL and PBL or lymphocytes from nontumorous kidney at the T-cell level with respect to clonogenic efficiency, phenotypic expression, and cytotoxicity.

¹ This work was supported in part by Grants CA-47891 and RR5511-27 from the NIH and the University Cancer Foundation.

² Present address: Investigation Drug Branch, CTEP/DCT/NCI, 6130 Executive Plaza North, Room 715B, Bethesda, MD 20892.

³ To whom requests for reprints should be addressed, at the Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 178, Houston, TX 77030.

Received 9/28/89. Revised 6/ 1/90.

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