TY - JOUR
T1 - Effects of systemic recombinant interleukin-2 on natural killer and lymphokine activated killer activity of human tumor infiltrating lymphocytes
AU - Anderson, Timothy M.
AU - Ibayashi, Yukihiro
AU - Tokuda, Yutaka
AU - Colquhoun, Steven D.
AU - Holmes, E. Carmack
AU - Golub, Sidney H.
PY - 1988/3
Y1 - 1988/3
N2 - The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxicity and to determine its modulation by the systemic administration of recombinant interleukin-2 (rIL-2). After preoperative systemic rIL-2, we extracted tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from patients with pulmonary tumors and compared pre-and posttreatment spontaneous NK activity and their response to in vitro rIL-2. Spontaneous TIL NK activity was increased in patients receiving 15,000 units/kg rIL-2 preoperatively (6.6 lytic units (LU)] compared to those receiving 1,000-10,000 units/kg (0.8 LU) or no rIL-2 (1.4 LU). After 3 days incubation with 1,000 units/ml rIL-2, TIL NK cytotoxic activity was increased in patients receiving 15,000 units/kg rlL-2 (65.4 LU) compared to those receiving 1,000-10,000 units/kg (6.0 LU) or no treatment (24.9 LU). Spontaneous TIL LAK activity was low overall (1.1 LU) with the exception of two patients receiving 15,000 units/kg who had 3.1 and 3.7 LU spontaneously. TIL LAK precursor activity was only slightly increased in patients receiving 1,000-10,000 units/kg rIL-2, whereas those receiving 15,000 units/kg rIL-2 had an average of 22.8 LU. Systemic rIL-2 also increased spontaneous PBL NK activity. Reincubation of PBL obtained at time of surgery or 3 days after discontinuing systemic rIL-2 resulted in significant increases in cytotoxic response to in vitro rIL-2 compared to pre-IL-2 in vitro responses. Systemic rIL-2 had no effect on spontaneous PBL LAK activity. Thus, the immunosuppressive tumor environment can be partially reversed with 15,000 units/ kg systemic rIL-2. Higher doses of systemic rIL-2 also increased spontaneous PBL NK activity at time of surgery and 3 days after discontinuing rIL-2. Both TIL and PBL inducible cytotoxicity were boosted in vitro following higher doses of systemic rIL-2.
AB - The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxicity and to determine its modulation by the systemic administration of recombinant interleukin-2 (rIL-2). After preoperative systemic rIL-2, we extracted tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from patients with pulmonary tumors and compared pre-and posttreatment spontaneous NK activity and their response to in vitro rIL-2. Spontaneous TIL NK activity was increased in patients receiving 15,000 units/kg rIL-2 preoperatively (6.6 lytic units (LU)] compared to those receiving 1,000-10,000 units/kg (0.8 LU) or no rIL-2 (1.4 LU). After 3 days incubation with 1,000 units/ml rIL-2, TIL NK cytotoxic activity was increased in patients receiving 15,000 units/kg rlL-2 (65.4 LU) compared to those receiving 1,000-10,000 units/kg (6.0 LU) or no treatment (24.9 LU). Spontaneous TIL LAK activity was low overall (1.1 LU) with the exception of two patients receiving 15,000 units/kg who had 3.1 and 3.7 LU spontaneously. TIL LAK precursor activity was only slightly increased in patients receiving 1,000-10,000 units/kg rIL-2, whereas those receiving 15,000 units/kg rIL-2 had an average of 22.8 LU. Systemic rIL-2 also increased spontaneous PBL NK activity. Reincubation of PBL obtained at time of surgery or 3 days after discontinuing systemic rIL-2 resulted in significant increases in cytotoxic response to in vitro rIL-2 compared to pre-IL-2 in vitro responses. Systemic rIL-2 had no effect on spontaneous PBL LAK activity. Thus, the immunosuppressive tumor environment can be partially reversed with 15,000 units/ kg systemic rIL-2. Higher doses of systemic rIL-2 also increased spontaneous PBL NK activity at time of surgery and 3 days after discontinuing rIL-2. Both TIL and PBL inducible cytotoxicity were boosted in vitro following higher doses of systemic rIL-2.
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M3 - Article
C2 - 3257716
AN - SCOPUS:0023872148
SN - 0008-5472
VL - 48
SP - 1180
EP - 1183
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -
