Functional and immunophenotypic modifications induced by interleukin-2 did not predict response to therapy in patients with renal cell carcinoma.
Twenty-five patients with renal cell carcinoma were treated with continuous infusion of IL-2 (3 x 10(6) units/m2/day) with or without lymphokine-activated killer (LAK) cells; 5 responded to therapy. Functional and immunophenotypic modifications of the peripheral blood lymphocytes (PBLs) did not predict response to therapy. Systemic administration of interleukin-2 (IL-2) during 5 days caused a preferential proliferation of natural killer (NK) cells, although CD4+ T cells remained the predominant circulating population, in particular in three of the five responding patients. The IL-2 low-affinity receptor was induced only on CD4+ T cells. B cells did not proliferate and immunoglobulin levels were not modified by IL-2. In the peripheral blood, the NK function increased but the LAK function in vivo remained low. The T-cell proliferative response in mixed lymphocyte cultures (MLCs) decreased after therapy. Four days of ex vivo culture of PBLs with IL-2 did not modify T and NK distributions, but increased the coexpression of CD8 on NK cells and NKH1 density; it decreased the coexpression of CD16 and induced LAK cell function. Three weeks after the end of the first course of therapy and before the second course was started, all immunological parameters returned to baseline levels, except the T-cell proliferative response in MLCs. The second course of IL-2 therapy induced the same modifications as the first one, with the exception of a higher CD4+ T-cell proliferation.
Favrot
M C
MC
Bone Marrow Transplant Unit, Centre Léon Bérard, Lyon, France.
Combaret
V
V
Negrier
S
S
Philip
I
I
Thiesse
P
P
Freydel
C
C
Bijmann
J T
JT
Franks
C R
CR
Mercatello
A
A
Philip
T
T
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000473:pathology*; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2