Caloric restriction (CR) is the leading non-pharmacological intervention to delay induced and spontaneous tumors in pre-clinical models. These effects of CR are largely attributed to canonical inhibition of pro-growth pathways. However, our recent data suggest that CR impairs primary tumor growth and cancer progression in the murine 4T1 model of triple negative breast cancer (TNBC), at least in part, through reduced frequency of the myeloid-derived suppressor cells (MDSC). In the present study, we sought to determine whether injection of excess MDSCs could block regression in 4T1 tumor growth and metastatic spread in BALB/cJ female mice undergoing daily CR. Our findings show that MDSC injection impeded CR-mediated protection against tumor growth without increasing lung metastatic burden. Overall, these results reveal that CR can slow cancer progression by affecting immune suppressive cells.

Impact statement: Inoculation of MDSCs from donor mice effectively impedes the ability of calorie restriction to protect against primary tumor growth without impacting lung metastatic burden in recipient animals.

热量限制 (CR) 是在临床前模型中延迟诱导性和自发性肿瘤的主要非药物干预。CR 的这些作用主要归因于对促生长途径的典型抑制。然而，我们最近的数据表明，在三阴性乳腺癌 (TNBC) 的小鼠 4T1 模型中，CR 会损害原发性肿瘤生长和癌症进展，至少部分是通过降低髓源性抑制细胞 (MDSC) 的频率。在本研究中，我们试图确定注射过量的 MDSC 是否可以阻止每天进行 CR 的 BALB/cJ 雌性小鼠 4T1 肿瘤生长和转移扩散的消退。我们的研究结果表明，MDSC 注射可在不增加肺转移负担的情况下阻碍 CR 介导的抗肿瘤生长保护作用。全面的，

影响声明：从供体小鼠接种 MDSCs 有效地阻碍了卡路里限制的能力，以防止原发性肿瘤生长，而不影响受体动物的肺转移负担。