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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 :
AuthorsEmailORCID
Annels, NEUNSPECIFIEDUNSPECIFIED
Shaw, VEUNSPECIFIEDUNSPECIFIED
Gabitass, RFUNSPECIFIEDUNSPECIFIED
Billingham, LUNSPECIFIEDUNSPECIFIED
Corrie, PUNSPECIFIEDUNSPECIFIED
Eatock, MUNSPECIFIEDUNSPECIFIED
Valle, JUNSPECIFIEDUNSPECIFIED
Smith, DUNSPECIFIEDUNSPECIFIED
Wadsley, JUNSPECIFIEDUNSPECIFIED
Cunningham, DUNSPECIFIEDUNSPECIFIED
Pandha, HUNSPECIFIEDUNSPECIFIED
Neoptolemos, JPUNSPECIFIEDUNSPECIFIED
Middleton, GUNSPECIFIEDUNSPECIFIED
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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