Figure 2 from Cell-Free DNA–Derived Immune Cell Ratios Uncover Cancer-Associated Systemic Changes

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Abstract
Cancer-associated shifts in immune cell contributions to cfDNA. A, Log2 FC (logFC) in cell type ranks grouped by category between healthy individuals (blue, n = 30) and patients with colorectal cancer (CRC; red, n = 124). Higher ranks reflect greater inferred cfDNA contribution. B, Comparison of median cell type ranks for monocytes (left) and lymphocytes (right) from the spleen, lymph node, blood, and thymus across ctDNA TF categories in CRC: ctDNA ND, ctDNA TF 1%. P values were calculated using two-sided Wilcoxon rank-sum tests. C, Correlation between cfDNA-derived ranks for effector CD4+ and CD8+ α–β T cells from lymph node and blood and T-cell fraction estimated using ImuneLENS (16) from germline WGS. Spearman’s correlation coefficient (r) and P value are shown. D, Same as in A, comparing healthy individuals (blue, n = 30) and patients with MIBC (yellow, n = 102). E, Same as B, for MIBC. F, Same as C, for MIBC. G, Volcano plot showing logFC in cfDNA-derived ranks vs. false discovery rate (FDR)-adjusted P values for individual immune cell types (monocytes, lymphocytes, and granulocytes) between healthy individuals (blue) and patients with CRC (red). Cell types with the highest FC are labeled. For cell types present in multiple tissues, only the instance with the highest log FC is shown. P values were calculated using two-sided Wilcoxon rank-sum tests and adjusted for multiple testing using the FDR method. H, Same as G, comparing healthy individuals and patients with MIBC (yellow). I, Receiver operating characteristic (ROC) curves for LASSO-regularized logistic regression models classifying CRC (red) and MIBC (yellow) vs. healthy controls. Models were trained on cell type ranks from monocytes, lymphocytes, and granulocytes, and evaluated using LOOCV. Area under the curve (AUC) and 95% CIs are indicated. Eff., effector; NS, not significant; Prog., progenitor; thy.-der., thymus-derived.