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Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival.

Donskov F, Bennedsgaard KM, Von Der Maase H, Marcussen N, Fisker R, Jensen JJ, Naredi P, Hokland M - Br. J. Cancer (2002)

Bottom Line: Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival.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.Confirmation of the results requires further studies including a larger number of patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dk

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.

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Monitoring of peripheral blood lymphocytes and lymphocyte subsets during interleukin-2 based immunotherapy. Median values for patients with partial responses (PR), stable disease (SD) and progressive disease (PD) are shown for (A): lymphocytes, (B): T-cells (CD3), (C): cytotoxic T-cells (CD8), (D): helper T-cells (CD4), (E): B-cells (CD20), (F): CD56 NK-cells and (G): CD57 NK-cells, respectively. Vertical and horizontal axes, 109 cells l−1 and weeks during immunotherapy, respectively.
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fig1: Monitoring of peripheral blood lymphocytes and lymphocyte subsets during interleukin-2 based immunotherapy. Median values for patients with partial responses (PR), stable disease (SD) and progressive disease (PD) are shown for (A): lymphocytes, (B): T-cells (CD3), (C): cytotoxic T-cells (CD8), (D): helper T-cells (CD4), (E): B-cells (CD20), (F): CD56 NK-cells and (G): CD57 NK-cells, respectively. Vertical and horizontal axes, 109 cells l−1 and weeks during immunotherapy, respectively.

Mentions: Baseline and on-treatment absolute number of lymphocytes and lymphocyte subsets defined by flow cytometry were examined and compared to responding (PR) and non-responding (SD+PD) patients. At baseline, no significant differences in responding patients compared to non-responding patients were demonstrated. Changes from baseline in the absolute number of lymphocytes and CD3 T-cells were detected in all patients. After 2 weeks of treatment, the absolute number of lymphocytes (P=0.028), CD3 T-cells (P=0.017) and CD57 NK cells (P=0.041) was significantly higher in responding patients compared with non-responding patients, Figure 1Figure 1


Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival.

Donskov F, Bennedsgaard KM, Von Der Maase H, Marcussen N, Fisker R, Jensen JJ, Naredi P, Hokland M - Br. J. Cancer (2002)

Monitoring of peripheral blood lymphocytes and lymphocyte subsets during interleukin-2 based immunotherapy. Median values for patients with partial responses (PR), stable disease (SD) and progressive disease (PD) are shown for (A): lymphocytes, (B): T-cells (CD3), (C): cytotoxic T-cells (CD8), (D): helper T-cells (CD4), (E): B-cells (CD20), (F): CD56 NK-cells and (G): CD57 NK-cells, respectively. Vertical and horizontal axes, 109 cells l−1 and weeks during immunotherapy, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376103&req=5

fig1: Monitoring of peripheral blood lymphocytes and lymphocyte subsets during interleukin-2 based immunotherapy. Median values for patients with partial responses (PR), stable disease (SD) and progressive disease (PD) are shown for (A): lymphocytes, (B): T-cells (CD3), (C): cytotoxic T-cells (CD8), (D): helper T-cells (CD4), (E): B-cells (CD20), (F): CD56 NK-cells and (G): CD57 NK-cells, respectively. Vertical and horizontal axes, 109 cells l−1 and weeks during immunotherapy, respectively.
Mentions: Baseline and on-treatment absolute number of lymphocytes and lymphocyte subsets defined by flow cytometry were examined and compared to responding (PR) and non-responding (SD+PD) patients. At baseline, no significant differences in responding patients compared to non-responding patients were demonstrated. Changes from baseline in the absolute number of lymphocytes and CD3 T-cells were detected in all patients. After 2 weeks of treatment, the absolute number of lymphocytes (P=0.028), CD3 T-cells (P=0.017) and CD57 NK cells (P=0.041) was significantly higher in responding patients compared with non-responding patients, Figure 1Figure 1

Bottom Line: Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival.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.Confirmation of the results requires further studies including a larger number of patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dk

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.

Show MeSH
Related in: MedlinePlus