Oncotarget

Research Papers:

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

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Oncotarget. 2015; 6:8261-8270. https://doi.org/10.18632/oncotarget.3014

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Abstract

Maria Napolitano1, Crescenzo D’Alterio1, Eleonora Cardone2, Anna Maria Trotta1, Biagio Pecori3, Daniela Rega2, Ugo Pace2, Dario Scala2, Giosuè Scognamiglio4, Fabiana Tatangelo4, Carmela Cacciapuoti5, Roberto Pacelli6, Paolo Delrio2, Stefania Scala1

1Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy

2Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy

3Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy

4Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy

5Trasfusional Service, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale” – I.R.C.C.S.-Naples, Italy

6Department 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−/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.


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