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外周髓源性抑制细胞和调节性T细胞PD-1阳性细胞可预测直肠癌患者对新辅助短程放疗的反应。

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

作者信息

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

机构信息

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.

出版信息

Oncotarget. 2015 Apr 10;6(10):8261-70. doi: 10.18632/oncotarget.3014.

DOI:10.18632/oncotarget.3014
PMID:25823653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4480750/
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.

摘要

短程术前放疗（SC-RT）联合全直肠系膜切除术（TME）是局部晚期直肠癌（LARC）患者的一种治疗选择。由于辐射诱导的DNA损伤可能影响肿瘤免疫原性，对13例接受SC-RT和TME治疗的LARC患者的髓源性抑制细胞（MDSCs）和调节性T细胞（Tregs）进行了评估。与健康供体（HD）相比，LARC患者外周血粒细胞性MDSCs（G-MDSC）[LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+]、单核细胞性（M-MDSC）[CD14+/HLA-DR-/lowCD11b+/CD33+]和Tregs[CD4+/CD25hi+/FOXP3+-CTLA-4/PD1]的基础值显著更高。在放疗后2周和5周（T2-T5）、手术前（T8）以及手术后6-12个月（T9、T10）评估外周血MDSC和Tregs。G-MDSC在T5时下降，在T8时进一步下降，而M-MDSC细胞在T5时下降；Tregs在T5时达到最低值。LARC无反应患者在SC-RT后M-MDSC显著减少，Treg-PD-1增加。在这项初步研究中，SC-RT治疗期间MDSCs和Tregs的减少可能代表LARC患者反应的生物标志物。需要进一步研究以证实治疗开始后5-8周内M-MDSC的最大程度减少和Treg-PD1细胞的增加可区分对SC-RT反应不佳的LARC患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/c3399a66143c/oncotarget-06-8261-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/b9455b20e6b4/oncotarget-06-8261-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/59744d66d610/oncotarget-06-8261-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/91ff8a697a6e/oncotarget-06-8261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/17c16db7871c/oncotarget-06-8261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/67432276b026/oncotarget-06-8261-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/c3399a66143c/oncotarget-06-8261-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/b9455b20e6b4/oncotarget-06-8261-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/59744d66d610/oncotarget-06-8261-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/91ff8a697a6e/oncotarget-06-8261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/17c16db7871c/oncotarget-06-8261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/67432276b026/oncotarget-06-8261-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97c/4480750/c3399a66143c/oncotarget-06-8261-g006.jpg

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