Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

Maria Napolitano, Crescenzo D'Alterio, Eleonora Cardone, Anna Maria Trotta, Biagio Pecori, Daniela Rega, Ugo Pace, Dario Scala, Giosuè Scognamiglio, Fabiana Tatangelo, Carmela Cacciapuoti, Roberto Pacelli, Paolo Delrio, Stefania Scala

Research output: Contribution to journalArticle

Abstract

Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6-12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

Original languageEnglish
Pages (from-to)8261-8270
Number of pages10
JournalOncotarget
Volume6
Issue number10
Publication statusPublished - 2015

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Keywords

  • MDSC
  • Radiotherapy
  • Rectal cancer
  • Treg

ASJC Scopus subject areas

  • Oncology

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