Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA.
Department of Health, Exercise & Sports Sciences, University of New Mexico, Albuquerque, NM 87131, USA.
Cells. 2022 Jun 10;11(12):1893. doi: 10.3390/cells11121893.
Immune cells can mount desirable anti-cancer immunity. However, some immune cells can support cancer disease progression. The presence of cancer can lead to production of immature myeloid cells from the bone marrow known as myeloid-derived suppressor cells (MDSCs). The immunosuppressive and pro-tumorigenic effects of MDSCs are well understood. Whether MDSCs are involved in promoting cancer cachexia is not well understood. We orthotopically injected the pancreas of mice with KPC cells or PBS. One group of tumor-bearing mice was treated with an anti-Ly6G antibody that depletes granulocytic MDSCs and neutrophils; the other received a control antibody. Anti-Ly6G treatment delayed body mass loss, reduced (TA) muscle wasting, abolished TA muscle fiber atrophy, reduced diaphragm muscle fiber atrophy of type IIb and IIx fibers, and reduced atrophic gene expression in the TA muscles. Anti-ly6G treatment resulted in greater than 50% Ly6G+ cell depletion efficiency in the tumors and TA muscles. These data show that, in the orthotopic KPC model, anti-Ly6G treatment reduces the number of Ly6G+ cells in the tumor and skeletal muscle and reduces skeletal muscle atrophy. These data implicate Ly6G+ cells, including granulocytic MDSCs and neutrophils, as possible contributors to the development of pancreatic cancer-induced skeletal muscle wasting.
免疫细胞可以产生理想的抗癌免疫。然而，一些免疫细胞可以支持癌症疾病的进展。癌症的存在会导致骨髓中产生不成熟的髓样细胞，称为髓源性抑制细胞（MDSCs）。MDSCs 的免疫抑制和促肿瘤作用已得到充分理解。但是，MDSCs 是否参与促进癌症恶病质尚不清楚。我们将 KPC 细胞或 PBS 原位注射到小鼠胰腺中。一组荷瘤小鼠接受抗 Ly6G 抗体治疗，该抗体耗尽粒细胞 MDSCs 和中性粒细胞；另一组接受对照抗体。抗 Ly6G 治疗延迟了体重减轻，减少了（TA）肌肉消耗，消除了 TA 肌肉纤维萎缩，减少了 IIb 和 IIx 纤维的膈肌肌纤维萎缩，并减少了 TA 肌肉中萎缩基因的表达。抗 Ly6G 治疗使肿瘤和 TA 肌肉中的 Ly6G+细胞耗竭效率超过 50%。这些数据表明，在原位 KPC 模型中，抗 Ly6G 治疗可减少肿瘤和骨骼肌中的 Ly6G+细胞数量，并减少骨骼肌萎缩。这些数据表明 Ly6G+细胞，包括粒细胞 MDSCs 和中性粒细胞，可能是胰腺癌诱导的骨骼肌消耗的发展的原因之一。
