Cancer Immunology, Immunotherapy

, Volume 63, Issue 2, pp 175–183 | Cite as

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

  • Nicola E. Annels
  • Victoria E. Shaw
  • Rachel F. Gabitass
  • Lucinda Billingham
  • Pippa Corrie
  • Martin Eatock
  • Juan Valle
  • David Smith
  • Jonathan Wadsley
  • David Cunningham
  • Hardev Pandha
  • John P. Neoptolemos
  • Gary Middleton
Original Article

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.

Keywords

Myeloid-derived suppressor cell Chemotherapy Gemcitabine Capecitabine Pancreatic
cancer 

Notes

Acknowledgments

This research was funded by BRIGHT: Better Research Into Gastrointestinal cancer Health and Treatment, registered charity number 1064857. The TeloVac Trial was funded by Cancer Research UK and KAEL-Gemvax.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2013_1502_MOESM1_ESM.pdf (54 kb)
Supplementary material 1 (PDF 53 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Nicola E. Annels
    • 1
  • Victoria E. Shaw
    • 2
  • Rachel F. Gabitass
    • 1
  • Lucinda Billingham
    • 3
  • Pippa Corrie
    • 4
  • Martin Eatock
    • 5
  • Juan Valle
    • 6
  • David Smith
    • 7
  • Jonathan Wadsley
    • 8
  • David Cunningham
    • 9
  • Hardev Pandha
    • 1
  • John P. Neoptolemos
    • 2
  • Gary Middleton
    • 3
  1. 1.University of SurreyGuildfordUK
  2. 2.Liverpool Cancer Research UK CentreLiverpoolUK
  3. 3.School of Cancer SciencesUniversity of BirminghamBirminghamUK
  4. 4.Addenbrookes HospitalCambridgeUK
  5. 5.Belfast City HospitalBelfastNorthern Ireland, UK
  6. 6.Christie HospitalManchesterUK
  7. 7.The Clatterbridge Cancer Centre NHS Foundation TrustWirralUK
  8. 8.Weston Park HospitalSheffieldUK
  9. 9.Royal Marsden HospitalSuttonUK

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