Regulatory effects of interleukin-7 on renal tumor infiltrating lymphocytes.
Biological therapy using a combination of lymphokine and tumor infiltrating lymphocytes (TILs) is a new approach to the treatment of patients with advanced cancer. To improve the potency of TILs, new cytokines with T-cell stimulatory effects used alone or in combination with interleukin-2 (IL-2) are currently being investigated. We have studied the effect of interleukin-7 (IL-7) on TILs derived from renal cell carcinoma. Our data demonstrated that five of ten TILs proliferated in response to IL-7 alone. This proliferative response was 73-90% less than that obtained with IL-2 alone. The use of IL-7 plus IL-2 resulted in a 1.2- to 4.7-fold increase in proliferation of six of ten TILs compared with IL-2 alone. IL-7-driven TIL growth was consistently blocked by anti-IL-2, anti-IL-2R and anti-IL-7 antibodies (37.2%, 41.6% and 82.2% suppression, respectively). The expression of IL-2 receptors was also significantly increased in the presence of IL-7 or IL-7 phytohemagglutinin (40.6 + 3.8 and 72.5 + 1.5). In comparison with IL-2, IL-7 treatment was associated with a decrease in CD56 (46.3% +/- 19 vs 10% +/- 4.9) and increase in CD3 (29.3% +/- 12 vs 73% +/- 6.4) and CD4 (19.3% +/- 15 vs 58% +/- 10). These studies suggest that in some renal TILs, IL-7 and IL-2 can have a synergistic proliferative effect. The IL-7 stimulatory effect appears to be mediated via both an IL-2 pathway and an IL-7-independent pathway.
Ditonno
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Immunotherapy Laboratory, UCLA School of Medicine.
Tso
C L
CL
Sakata
T
T
deKernion
J B
JB
Belldegrun
A
A
D015703:Antigens, CD; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D004357:Drug Synergism; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D015703:Antigens, CD; D007376:Interleukin-2; D015851:Interleukin-7; D015375:Receptors, Interleukin-2