title: Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival.
abstract: The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-alpha and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients.
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dk
authors.forename: F
authors.initials: F
authors.lastname: Donskov
authors.forename: K M
authors.initials: KM
authors.lastname: Bennedsgaard
authors.forename: H
authors.initials: H
authors.lastname: Von Der Maase
authors.forename: N
authors.initials: N
authors.lastname: Marcussen
authors.forename: R
authors.initials: R
authors.lastname: Fisker
authors.forename: J J
authors.initials: JJ
authors.lastname: Jensen
authors.forename: P
authors.initials: P
authors.lastname: Naredi
authors.forename: M
authors.initials: M
authors.lastname: Hokland
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015993:Life Tables; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D016246:Lymphocytes, Tumor-Infiltrating / Q000145:classification*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2