Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients
Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients(420 views) Napolitano M, D'Alterio C, Cardone E, Trotta AM, Pecori B, Rega D, Pace U, Scala D, Scognamiglio G, Tatangelo F, Cacciapuoti C, Pacelli R, Delrio P, Scala S
Keywords: Mdsc, Radiotherapy, Rectal Cancer, Treg, Cd11b Antigen, Cd14 Antigen, Cd15 Antigen, Cd33 Antigen, Cd4 Antigen, Cytotoxic T Lymphocyte Antigen 4, Hla Dr Antigen, Interleukin 2 Receptor Alpha, Programmed Death 1 Receptor, Transcription Factor Foxp3, Adult, Advanced Cancer, Aged, Article, Cancer Adjuvant Therapy, Clinical Article, Controlled Study, Female, Granulocytic Myeloid Derived Suppressor Cell, Human, Human Cell, Human Tissue, Middle Aged, Monocytic Myeloid Derived Suppressor Cell, Pilot Study, Postoperative Period, Prediction, Preoperative Period, Preoperative Radiotherapy, Radiation Response, Rectum Cancer, Rectum Surgery, Regulatory T Lymphocyte, Short Course Preoperative Radiotherapy, Total Mesorectal Excision, Treatment Response, Very Elderly,
Affiliations: *** IBB - CNR ***
Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', I.R.C.C.S., Naples, Italy
Colorectal Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', I.R.C.C.S., Naples, Italy
Radiotherapy, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', I.R.C.C.S., Naples, Italy
Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', I.R.C.C.S., Naples, Italy
Trasfusional Service, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale', I.R.C.C.S., Naples, Italy
Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Istituto di Biostrutture e Bioimmagini - C.N.R., Naples, Italy
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Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients
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.
Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients
Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients