title: Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients.
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.
authors.affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Crescenzo
authors.initials: C
authors.lastname: D'Alterio
authors.affiliation: Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cardone
authors.affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Trotta
authors.affiliation: Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Pecori
authors.affiliation: Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rega
authors.affiliation: Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pace
authors.affiliation: Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Scala
authors.affiliation: Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Giosuè
authors.initials: G
authors.lastname: Scognamiglio
authors.affiliation: Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.affiliation: Trasfusional Service, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Cacciapuoti
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University School of Medicine, and Istituto di Biostrutture e Bioimmagini - C.N.R., Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacelli
authors.affiliation: Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Delrio
authors.affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000528:radiation effects; D020360:Neoadjuvant Therapy; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: MDSC; Treg; radiotherapy; rectal cancer
references.citation: Cancer Res. 2013 Jul 15;73(14):4233-46
references.pmid: 23722542
references.citation: Eur J Immunol. 2010 Nov;40(11):2969-75
references.pmid: 21061430
references.citation: Cancer Immunol Immunother. 2009 Jan;58(1):49-59
references.pmid: 18446337
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4275-80
references.pmid: 20160101
references.citation: Cytometry B Clin Cytom. 2013 Sep-Oct;84(5):291-308
references.pmid: 24022852
references.citation: EMBO J. 1992 Nov;11(11):3887-95
references.pmid: 1396582
references.citation: Nat Rev Cancer. 2007 Nov;7(11):880-7
references.pmid: 17957190
references.citation: N Engl J Med. 2001 Aug 30;345(9):638-46
references.pmid: 11547717
references.citation: Cancer Immunol Immunother. 2014 Jan;63(1):29-36
references.pmid: 24052136
references.citation: Radiother Oncol. 2008 Jun;87(3):343-9
references.pmid: 18093674
references.citation: J Clin Invest. 2010 Mar;120(3):694-705
references.pmid: 20179352
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Int Immunol. 2009 Sep;21(9):1065-77
references.pmid: 19651643
references.citation: Nat Rev Immunol. 2012 Apr;12(4):253-68
references.pmid: 22437938
references.citation: World J Gastroenterol. 2012 Jul 7;18(25):3303-9
references.pmid: 22783056
references.citation: Front Oncol. 2012 Oct 26;2:153
references.pmid: 23112958
references.citation: Nat Rev Immunol. 2009 Mar;9(3):162-74
references.pmid: 19197294
references.citation: Science. 2008 Oct 10;322(5899):271-5
references.pmid: 18845758
references.citation: J Exp Med. 2009 Aug 3;206(8):1717-25
references.pmid: 19581407
references.citation: Histopathology. 2005 Aug;47(2):141-6
references.pmid: 16045774
references.citation: Front Oncol. 2014 Jan 21;4:1
references.pmid: 24478982
references.citation: J Clin Invest. 2014 Feb;124(2):687-95
references.pmid: 24382348
references.citation: Nat Rev Cancer. 2012 Apr;12(4):252-64
references.pmid: 22437870
references.citation: Cancer Res. 2004 Feb 1;64(3):1140-5
references.pmid: 14871849
references.citation: Cancer Res. 2011 Feb 15;71(4):1263-71
references.pmid: 21303976
references.citation: Lancet. 2005 Jan 8-14;365(9454):153-65
references.pmid: 15639298
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: J Exp Med. 2000 Oct 2;192(7):1027-34
references.pmid: 11015443
references.citation: Ann Surg Oncol. 2012 Nov;19(12):3706-12
references.pmid: 22669453
references.citation: N Engl J Med. 1997 Apr 3;336(14):980-7
references.pmid: 9091798
references.citation: Br J Surg. 2006 Oct;93(10):1215-23
references.pmid: 16983741
references.citation: BMC Cancer. 2013;13:279
references.pmid: 23742033
references.citation: N Engl J Med. 2004 Oct 21;351(17):1731-40
references.pmid: 15496622
references.citation: Cancer Res. 2013 Dec 1;73(23):6900-12
references.pmid: 23975756
references.citation: J Leukoc Biol. 2009 Jun;85(6):996-1004
references.pmid: 19261929
references.citation: Cancer Res. 2010 Jan 1;70(1):68-77
references.pmid: 20028852
references.citation: Immunol Rev. 2006 Aug;212:8-27
references.pmid: 16903903
references.citation: J Natl Cancer Inst. 2013 Feb 20;105(4):256-65
references.pmid: 23291374
references.citation: Br J Surg. 2012 Apr;99(4):577-83
references.pmid: 22241246
references.citation: Nat Med. 2002 Aug;8(8):793-800
references.pmid: 12091876
references.citation: Nat Rev Cancer. 2005 Nov;5(11):867-75
references.pmid: 16327765
references.citation: Immunity. 2009 May;30(5):636-45
references.pmid: 19464986