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

// Maria Napolitano 1 , Crescenzo D’Alterio 1 , Eleonora Cardone 2 , Anna Maria Trotta 1 , Biagio Pecori 3 , Daniela Rega 2 , Ugo Pace 2 , Dario Scala 2 , Giosue Scognamiglio 4 , Fabiana Tatangelo 4 , Carmela Cacciapuoti 5 , Roberto Pacelli 6 , Paolo Delrio 2 , Stefania Scala 1 1 Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 2 Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 3 Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 4 Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 5 Trasfusional Service, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy 6 Department of Advanced Biomedical Sciences, Federico II University School of Medicine, and Istituto di Biostrutture e Bioimmagini – C.N.R., Naples, Italy Correspondence to: Stefania Scala, e-mail: scalaste@gmail.it ; s.scala@istitutotumori.na.it Keywords: MDSC, Treg, radiotherapy, rectal cancer Received: November 03, 2014 Accepted: December 31, 2014 Published: January 21, 2015 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 −/low CD11b + /CD33 + ] and Tregs [CD4 + /CD25 hi+ /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.