Siemińska Izabela, Węglarczyk Kazimierz, Walczak Marta, Czerwińska Agata, Pach Radosław, Rubinkiewicz Mateusz, Szczepanik Antoni, Siedlar Maciej, Baran Jarek
Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Wielicka str. 265, Krakow 30-663, Poland.
First Department of General Surgery, Jagiellonian University Medical College, M. Jakubowskiego str. 2, Krakow 30-688, Poland.
Transl Oncol. 2022 Mar;17:101346. doi: 10.1016/j.tranon.2022.101346. Epub 2022 Jan 21.
Colorectal cancer (CRC) is the third most common malignancy. Its development and progression is associated with natural immunosuppression related, among others, to myeloid derived suppressor cells (MDSCs). Overall, 54 patients in different stage of CRC, before any treatment were recruited into the study. The analysis included flow cytometry evaluation of blood MDSCs subsets, correlation their level with the tumor stage and T cell subsets. In the case of 11 patients, MDSCs level was evaluated before and 3 days after surgery, and these patients were monitored for cancer recurrence over 5 years. The results showed that frequency of circulating MDSCs subsets is increased significantly in CRC patients, with highest level detected in most advanced tumor stages. Moreover, only monocytic MDSCs (Mo-MDSCs) positively correlate with regulatory Treg, and negatively with tumor Her2/neu specific CD8+ T cells. Circulating MDSCs, in contrast to tumor resident (mostly Mo-MDSCs), are negative for PD-L1 expression. Additionally, after surgery the blood level of Mo-MDSCs increases significantly, and this is associated with tumor recurrence during a 5-year follow-up. In conclusion, Mo-MDSCs are pivotal players in CRC-related immunosuppression and may be associated with the risk of tumor recurrence after surgery.
结直肠癌(CRC)是第三大常见恶性肿瘤。其发生和发展与自然免疫抑制相关,其中包括与髓源性抑制细胞(MDSC)有关。总体而言,54例处于不同阶段的未经任何治疗的CRC患者被纳入该研究。分析包括对血液中MDSC亚群的流式细胞术评估、其水平与肿瘤分期及T细胞亚群的相关性。对于11例患者,在手术前及手术后3天评估MDSC水平,并对这些患者进行了5年的癌症复发监测。结果显示,CRC患者循环MDSC亚群的频率显著增加,在最晚期肿瘤阶段检测到的水平最高。此外,只有单核细胞MDSC(Mo-MDSC)与调节性Treg呈正相关,与肿瘤Her2/neu特异性CD8+T细胞呈负相关。与肿瘤驻留细胞(主要是Mo-MDSC)相比,循环MDSC的PD-L1表达呈阴性。此外,手术后Mo-MDSC的血液水平显著升高,这与5年随访期间的肿瘤复发相关。总之,Mo-MDSC是CRC相关免疫抑制的关键参与者,可能与手术后肿瘤复发风险相关。