Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma.
Previous studies have documented the effects of IL2 on the growth and effector function of tumor-infiltrating lymphocytes (TIL) in cancer patients. Since IL7 is known to induce T- and NK-cell responses in the peripheral blood, we examined the immuno-enhancing effects of IL7 on TIL derived from human renal-cell carcinoma (RCC). Whereas IL2 induced the growth of freshly isolated TIL in vitro, IL7 was ineffective alone and failed to increase the total number of cells proliferating to IL2. However, IL7 did provide a proliferative signal to TIL that were initially expanded in culture with either IL2 or IL2/IL7 for 2 weeks. IL7 also induced the proliferation of CD4+ and CD8+ TIL lines that have specificity for RCC. The proliferative response induced by IL7 was independent of IL2, since anti-IL2 antibodies did not block IL7-induced proliferation of TIL. IL7 did cooperate with anti-CD3 stimulation for the induction of proliferation; however, the magnitude of this interaction was variable and the response usually additive. In addition, IL7 synergized with anti-CD3 to induce the secretion of IFN gamma from short-term-cultured TIL and from a TIL line. Although IL7 did not promote the development of a tumor-specific T-cell response from IL2-expanded TIL, IL7 enhanced lymphokine-activated killer (LAK) activity from some short-term-cultured TIL. These results illustrate that IL7 can potentiate the growth and production of IFN gamma from RCC-reactive TIL and, to a lesser extent, enhance IL2-induced LAK activity of TIL.
Sica
D
D
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
Rayman
P
P
Stanley
J
J
Edinger
M
M
Tubbs
R R
RR
Klein
E
E
Bukowski
R
R
Finke
J H
JH
D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D015851:Interleukin-7; D007371:Interferon-gamma