Clonal analysis of lymphocytes from tumor, peripheral blood, and nontumorous kidney in primary renal cell carcinoma

Abstract

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 (greater than or equal to 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 less than 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.(ABSTRACT TRUNCATED AT 400 WORDS)