The Effect of Sunitinib on Immune Subsets in Metastatic Clear Cell Renal Cancer

TY - JOUR

T1 - The Effect of Sunitinib on Immune Subsets in Metastatic Clear Cell Renal Cancer

AU - Powles, Thomas

AU - Chowdhury, Simon

AU - Bower, Mark

AU - Saunders, Nataile

AU - Lim, Louise

AU - Shamash, Jonathan

AU - Sarwar, Naveed

AU - Sadev, Anju

AU - Peters, John

AU - Green, James

AU - Boleti, Katia

AU - Augwal, Samir

PY - 2011

Y1 - 2011

N2 - Background: Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is associated with leucopenia; however, its effects on specific immune cell subsets are unclear. Alterations in immune cell subsets may contribute to tumour progression. Methods: Lymphocyte subsets (CD3, 4, 8, 19 and 56) were measured in 43 untreated MCRC patients who received sunitinib. The protocol included a structured treatment interruption of 5 weeks. Cell populations were measured at specific time points during sunitinib treatment and the treatment break. Results: Sunitinib was associated with significant declines in total leucocyte (-48%), neutrophil (-62%), CD3 total T cell (-31%) and CD4 counts (32%; p <0.05). There was no significant change in CD19 B lymphocyte, CD8 or CD56 natural killer cells. During the sunitinib-free interval, all parameters recovered to baseline. No patients developed opportunistic infections or neutropenic sepsis. The level of specific immune subsets at presentation or occurrence of a fall in specific counts had an effect on progression-free survival (p > 0.05). Conclusions: Sunitinib is associated with reversible inhibition of specific lymphocyte subsets which has implications for the immunological control of MCRC and its use in combination with other agents. Despite suppressive effects, there was no evidence of predisposition to immune suppressive-related infection. Copyright (C) 2010 S. Karger AG, Basel

AB - Background: Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is associated with leucopenia; however, its effects on specific immune cell subsets are unclear. Alterations in immune cell subsets may contribute to tumour progression. Methods: Lymphocyte subsets (CD3, 4, 8, 19 and 56) were measured in 43 untreated MCRC patients who received sunitinib. The protocol included a structured treatment interruption of 5 weeks. Cell populations were measured at specific time points during sunitinib treatment and the treatment break. Results: Sunitinib was associated with significant declines in total leucocyte (-48%), neutrophil (-62%), CD3 total T cell (-31%) and CD4 counts (32%; p <0.05). There was no significant change in CD19 B lymphocyte, CD8 or CD56 natural killer cells. During the sunitinib-free interval, all parameters recovered to baseline. No patients developed opportunistic infections or neutropenic sepsis. The level of specific immune subsets at presentation or occurrence of a fall in specific counts had an effect on progression-free survival (p > 0.05). Conclusions: Sunitinib is associated with reversible inhibition of specific lymphocyte subsets which has implications for the immunological control of MCRC and its use in combination with other agents. Despite suppressive effects, there was no evidence of predisposition to immune suppressive-related infection. Copyright (C) 2010 S. Karger AG, Basel

KW - Sunitinib

KW - Immune parameters

KW - Renal cancer

KW - CARCINOMA PATIENTS

KW - INTERFERON-ALPHA

KW - IMMUNOTHERAPY

KW - THERAPY

U2 - 10.1159/000319498

DO - 10.1159/000319498

M3 - Article

SN - 0042-1138

VL - 86

SP - 53

EP - 59

JO - Urologia Internationalis

JF - Urologia Internationalis

IS - 1

ER -