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The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer.

Annels, NE, Shaw, VE, Gabitass, RF, Billingham, L, Corrie, P, Eatock, M, Valle, J, Smith, D, Wadsley, J, Cunningham, D , Pandha, H, Neoptolemos, JP and Middleton, G (2013) The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. Cancer Immunol Immunother.

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Abstract

In pre-clinical models, the only two chemotherapy drugs which have been demonstrated to directly reduce the number of myeloid-derived suppressor cells (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We found no evidence that gemcitabine and capecitabine directly reduce MDSC% in patients. Gemcitabine and capecitabine reduced MDSCs in 42 % of patients (n = 19) and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8 patients with minimal tumour volume change on treatment, the MDSC% went up: increases in MDSC% in these patients appeared to correlate with sustained cancer-related inflammatory cytokine upregulation. In a separate cohort of 21 patients treated with gemcitabine and capecitabine together with concurrently administered GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there was a significant difference in the trajectory of MDSCs between those receiving GV1001 and GM-CSF in combination with chemotherapy and those receiving chemotherapy alone. Thus, there was no evidence that the addition of low-dose adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination MDSC levels. A high pre-vaccination MDSC% does not preclude the development of immunity to a tumour-associated antigen.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences
Authors :
NameEmailORCID
Annels, NE
Shaw, VE
Gabitass, RF
Billingham, L
Corrie, P
Eatock, M
Valle, J
Smith, D
Wadsley, J
Cunningham, D
Pandha, H
Neoptolemos, JP
Middleton, G
Date : 29 November 2013
Identification Number : 10.1007/s00262-013-1502-y
Related URLs :
Additional Information : The original publication is available at http://link.springer.com/article/10.1007%2Fs00262-013-1502-y
Depositing User : Symplectic Elements
Date Deposited : 28 Nov 2014 15:45
Last Modified : 29 Nov 2014 02:33
URI: http://epubs.surrey.ac.uk/id/eprint/806602

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