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dc.contributor.authorAnnels, N
dc.contributor.authorShaw, V
dc.contributor.authorGabitass, R
dc.contributor.authorBillingham, L
dc.contributor.authorCorrie, P
dc.contributor.authorEatock, M
dc.contributor.authorValle, Juan W
dc.contributor.authorSmith, D
dc.contributor.authorWadsley, J
dc.contributor.authorCunningham, D
dc.contributor.authorPandha, H
dc.contributor.authorNeoptolemos, J
dc.contributor.authorMiddleton, G
dc.date.accessioned2014-04-17T08:27:39Z
dc.date.available2014-04-17T08:27:39Z
dc.date.issued2014-02
dc.identifier.citationThe 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. 2014, 63 (2):175-83 Cancer Immunol Immunotheren
dc.identifier.issn1432-0851
dc.identifier.pmid24292263
dc.identifier.doi10.1007/s00262-013-1502-y
dc.identifier.urihttp://hdl.handle.net/10541/315941
dc.description.abstractIn 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.
dc.language.isoenen
dc.rightsArchived with thanks to Cancer immunology, immunotherapy : CIIen
dc.subject.meshAntigens, CD11b
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshDeoxycytidine
dc.subject.meshFluorouracil
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor
dc.subject.meshHumans
dc.subject.meshInterleukin-6
dc.subject.meshMyeloid Cells
dc.subject.meshPancreatic Neoplasms
dc.subject.meshPeptide Fragments
dc.subject.meshTelomerase
dc.subject.meshVaccination
dc.titleThe 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.en
dc.typeArticleen
dc.contributor.departmentCentre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, Franceen
dc.identifier.journalCancer Immunology, Immunotherapyen
html.description.abstractIn 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.


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