Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.

As additional validation supporting the role of myeloid-derived cells, and specifically monocytes, as a dominant contributor to plasma CyC levels, we found a significant positive correlation between blood monocyte counts and CyC residual in the UKB cohort ( Figure S4 B; multivariate regression), and two-sample Mendelian randomization using blood-derived CST3 eQTLs (eQTLGen 58 ) as exposure identified a highly significant positive association with CyC production (p = 6.13e−77; Figure 4 E).

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