The effect of sunitinib on immune subsets in metastatic clear cell renal cancer.
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.
Powles
Thomas
T
St Bartholomew Hospital, London, UK. thomas.powles@bartsandthelondon.nhs.uk
Chowdhury
Simon
S
Bower
Mark
M
Saunders
Nataile
N
Lim
Louise
L
Shamash
Jonathan
J
Sarwar
Naveed
N
Sadev
Anju
A
Peters
John
J
Green
James
J
Boleti
Katia
K
Augwal
Samir
S
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007680:Kidney Neoplasms; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib