Table 2.
Profile of blood markers in study patients and healthy controls.
| Patients at baseline vs. ctrl (n=15) | Levels under treatment | LR vs. RP 1 | irAE | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Marker | untreated | pretreated | 2+L-IO vs. untreated(n=204) | ICT (vs. baseline) | 1L-IO (vs. baseline) | 2+L-IO (vs. baseline) | baseline 1 | under treatment | baseline vs. ctrl 1 | |||||||||
| all 1L(n=154) | ICT(n=108) | 1L-IO(n=46) | 2+L-IO(n=50) | C1 vs. bl(n=27) | C4 vs bl(n=67) | PD vs. C4(n=10) | C1(n=11) | C4(n=28) | PD vs. C4(n=6) | C4(n=26) | PD vs. C4(n=9) | C1 1 | C4 1 | PD 1 | ||||
| IL-1β | FC>10 p=0.055 |
FC>10 p=0.028 |
FC>10 p=0.202 |
FC>10 p=0.157 |
FC=0.2 p=0.316 |
FC=1 p=1 |
FC=1.2 p=0.959 |
FC<0.1 p=0.18 |
FC<0.1 p=0.317 |
FC=14 p=0.593 |
FC=1 p=1 |
FC=0.1 p=0.655 |
FC=1 p=1 |
FC=0.8-3 p>0.5 |
FC=1 p>0.5 |
FC=1.4-10 p>0.07 |
FC=0.1-10 p>0.3 |
FC=7 p=0.009$ |
| IL-2 | FC=3 p=0.328 |
FC=4 p=0.397 |
FC=1.4 p=0.265 |
FC=0.7 p=0.024 |
FC=0.2 p=0.005 |
FC=0.5 p=0.18 |
FC=0.8 p=0.674 |
FC<0.1 p=0.18 |
FC=0.3 p=0.317 |
FC=27 p=0.317 |
FC=1 p=1 |
FC=0.7 p=0.686 |
FC<0.1 p=0.317 |
FC=0.8-9 p=>0.2 |
FC>10 p>0.35 |
FC=0.5-10 p>0.6 |
FC<0.1-1 p>0.4 |
FC=0.1-4 p>0.1 |
| IL-4 | FC=148 p=0.128 |
FC=225 p=0.104 |
FC=1.8 p=0.241 |
FC=4 p=0.121 |
FC<0.1 p=0.804 |
FC=0.1 p=0.109 |
FC<0.1 p=0.019 |
FC<0.1 p=0.109 |
FC=0.6 p=0.715 |
FC=7 p=0.786 |
FC=0.1 p=0.285 |
FC=1.3 p=0.753 |
FC=0.3 p=0.18 |
FC=0.5-49 p>0.5 |
FC>10 p>0.40 |
FC=0.2-10 p>0.1 |
FC=0.7-10 p>0.3 |
FC=1.7-88 p>0.06 |
| IL-5 | FC=7 p=0.052 | FC=6 p=0.052 |
FC=10 p=0.073 |
FC=2 p=0.32 |
FC=0.3 p=0.180 |
FC<0.1 p=0.08 |
FC=1.1 p=0.701 |
FC<0.1 p=0.285 |
FC=0.3 p=0.273 |
FC=1.4 p=0.61 |
FC<0.1 p=0.317 |
FC=2 p=0.686 |
FC=1 p=1 |
FC=3-213 p=0.03-0.5 |
FC<0.1-10 p>0.4 |
FC=6-10 p>0.19 |
FC<0.1-1 p>0.8 |
FC=4 p=0.011$
FC=17 p=0.003# |
| IL-6 | FC=31 p=0.0002 | FC=20 p=0.004 | FC=56 p=10-6 | FC=49 p=5E-06 | FC=1.6 p=0.0007 |
FC=0.2 p=0.002 |
FC=6 p=0.695 |
FC=0.6 p=0.508 |
FC=0.8 p=0.575 |
FC=0.5 p=0.043 | FC=0.4 p=0.5 |
FC=0.5 p=0.086 |
FC=2 p=0.327 |
FC=0.7 p=0.005$ |
FC=0.1-0.8 p>0.4 |
FC<0.1-2 p>0.11 |
FC=0.1-12 p>0.11 |
FC=0.4-1 p>0.2 |
| IL-8 | FC=25 p=4E-08 | FC=17 p=1E-07 | FC=42 p=3x10-7 |
FC=34 p=7x10-8 | FC=1.4 p=0.052 |
FC=0.3 p=0.003 |
FC=0.7 p=0.025 |
FC=0.5 p=0.799 |
FC=0.5 p=0.062 |
FC=0.4 p=0.179 |
FC=0.5 p=0.345 |
FC=0.7 p=0.238 |
FC=3 p=0.314 |
FC=0.7 p=0.02-0.6 |
FC=1.7-1.9 p>0.16 |
FC=0.5-1.4 p>0.3 |
FC=0.6-4 p>0.13 |
FC=1.6 p=0.028 $ |
| IL-10 | FC=11 p=0.0002 | FC=11 p=3E-04 | FC=11 p=4x10-4 |
FC=9 p=4E-06 |
FC=0.3 p=0.231 |
FC=1.3 p=0.314 |
FC=1.7 p=0.215 |
FC<0.1 p=0.08 |
FC=3 p=1 |
FC=1.3 p=0.913 |
FC=0.5 p=0.273 |
FC=1.3 p=0.753 |
FC=0.7 p=0.893 |
FC=1-2 p>0.4 |
FC=0.7-10 p>0.2 |
FC=0.4-7 p>0.2 |
FC<0.1-10 p=0.03-0.7 |
FC=3 p=0.004 $ |
| IP-10 | FC=1.4 p=0.497 |
FC=1.1 p=0.688 |
FC=2 p=0.006 | FC=2 p=0.006 | FC=1.4 p=0.011 |
FC=1.7 p=0.349 |
FC=1.7 p=0.001 |
FC=0.9 p=0.575 |
FC=3 p=0.062 |
FC=1.4 p=0.031 | FC=0.6 p=0.075 |
FC=0.9 p=0.159 |
FC=2 p=0.314 |
FC=0.7-0.8 p=0.04-0.4 |
FC=0.2-1.5 p>0.1 |
FC=0.3-0.7 p>0.1 |
FC=0.6-1.4 p>0.1 |
FC=0.6-1.4 p>0.1 |
| IL-12p70 | FC=1.2 p=0.954 |
FC=1.3 p=0.689 |
FC=1.2 p=0.519 |
FC=0.4 p=0.397 |
FC=0.3 p=0.253 |
FC=0.5 p=0.012 |
FC=0.8 p=0.638 |
FC=0.2 p=0.144 |
FC=0.3 p=0.465 |
FC=1.6 p=0.893 |
FC=1 p=1 |
FC=7 p=0.593 |
FC>10 p=0.18 |
FC=0.4 p>0.05 |
FC>10 p>0.2 |
FC=0.6->10 p>0.3 |
FC=1-17 p>0.4 |
FC=4 p=0.019$ FC=9 p=0.014# |
| IL-17F | FC>10 p=0.529 |
FC>10 p=0.515 |
FC>10 p=0.421 |
FC>10 p=0.584 |
FC=0.01 p=0.805 |
FC=1 p=1 |
FC<0.1 p=0.317 |
FC=1 p=1 |
FC=1 p=1 |
FC=46 p=0.285 |
FC=1 p=1 |
FC<0.1 p=0.317 |
FC=1 p=1 |
FC>10 p>0.19 |
FC=1 p=1 |
FC=1->10 p>0.5 |
FC=1 p=1 |
FC<0.1-10 p=0.5-0.4 |
| CCL5 | FC=1.4 p=0.026 | FC=1.4 p=0.016 | FC=1.2 p=0.132 |
FC=1.9 p=0.001 |
FC=1.4 p=0.002 |
FC=1.2 p=0.088 |
FC=1.05 p=0.358 | FC=0.9 p=0.646 |
FC=0.9 p=0.79 |
FC=1.1 p=0.767 |
FC=0.7 p=0.463 |
FC=0.7 p=0.012 | FC=1.1 p=0.374 |
FC=0.8-1.1 p>0.17 |
FC=0.9-1.1 p>0.4 |
FC=0.7-0.8 p>0.07 |
FC=8-1.2 p>0.3 |
FC=0.7-0.9 p>0.08 |
| sCD40L | FC=0.9 p=0.141 |
FC=0.9 p=0.228 |
FC=0.8 p=0.092 |
FC=1 p=0.213 |
FC=1.1 p=0.859 |
FC=1.1 p=0.829 |
FC=1 p=0.336 |
FC=1.1 p=0.114 | FC=0.5 p=0.003 | FC=1 p=0.946 |
FC=0.8 p=0.753 |
FC=1 p=0.581 |
FC=1 p=0.767 |
FC=0.7-1.1 p=0.05-0.7 |
FC=0.6-1.9 p>0.1 |
FC=0.5-1.1 p>0.1 |
FC=1.1-1.3 p>0.1 |
FC=0.5-1.2 p=0.01-0.6 |
| G-CSF | FC=5 p=0.004 | FC=6 p=10-4 |
FC=2 p=0.564 |
FC=1.6 p=0.297 |
FC=0.3 p=0.008 |
FC=2 p=0.001 |
FC=0.4 p=0.733 |
FC=0.6 p=0.285 | FC=0.9 p=0.328 |
FC=1.3 p=0.889 |
FC=0.2 p=0.116 |
FC=1 p=0.689 |
FC=1.7 p=0.213 |
FC=0.4-1.5 p>0.3 |
FC=0.7-1.7 p>0.2 |
FC=0.5-0.8 p>0.2 |
FC=0.3-1.7 p=0.05-0.4 |
FC=0.7 p=0.027$ |
| Granzyme A | FC=1.5 p=0.903 |
FC=1.7 p=0.567 |
FC=1 p=0.384 |
FC=1 p=0.72 |
FC=0.7 p=0.691 |
FC=0.8 p=0.049 |
FC=0.7 p=0.797 |
FC=0.9 p=0.799 |
FC=1.5 p=0.594 |
FC=1 p=0.716 |
FC=0.2 p=0.249 |
FC=0.5 p=0.551 |
FC=1.4 p=0.314 |
FC=0.5-2 p>0.1 |
FC=0.8-1.9 p>0.08 |
FC=0.9-2 p>0.1 |
FC=0.2-0.6 p>0.1 |
FC=1.3 p=0.003# |
| ICAM-1 | FC=261 p=9x10-7 | FC=326 p=4x10-7 |
FC=110 p=0.0001 | FC=2839 p=9x10-7 | FC=11 p=0.011 |
FC=0.3 p=0.203 |
FC=0.3 p=0.0005 | FC=0.8 p=0.59 | FC=0.6 p=0.003 | FC=0.7 p=0.317 | FC=0.2 p=0.917 |
FC=8 p=0.0004 |
FC=0.2 p=0.008 | FC<0.1-2 p>0.1 |
FC=0.2-1.8 p>0.03 |
FC<0.1-24 p>0.15 |
FC=2-9 p>0.01 |
FC=0.1-0.5 p>0.2 |
| IFN-γ | FC>10 p=0.603 |
FC>10 p=0.65 |
FC>10 p=0.382 |
FC>10 p=0.494 |
FC=3 p=0.641 |
FC=1 p=1 |
FC=1 p=1 |
FC=1 p=1 |
FC=1 p=1 |
FC=4 p=0.317 |
FC=1 p=1 |
FC=1 p=1 |
FC=1 p=1 |
FC>10 p>0.2 |
FC=1 p=1 |
FC=1->10 p>0.6 |
FC=1 p=1 |
FC<0.1-10 p>0.1 |
| TNF | FC=14 p=0.829 |
FC=20 p=0.995 |
FC=2 p=0.587 |
FC=3 p=0.869 |
FC=0.2 p=0.488 |
FC=0.6 p=0.136 |
FC=0.5 p=0.039 |
FC=0.4 p=0.345 |
FC=0.5 p=0.779 |
FC=23 p=0.695 |
FC=9 p=0.109 |
FC=1.2 p=0.79 |
FC=1.2 p=0.5 |
FC=0.8.8 p>0.5 |
FC=1.2-10 p>0.09 |
FC=0.2-20 p>0.19 |
FC=0.3-4 p=0.044-1 |
FC=0.1-6 p=0.02-0.9 |
| TNF-RI | FC=1.6 p=0.021 | FC=1.5 p=0.03 | FC=1.8 p=0.021 | FC=1.7 p=0.001 |
FC=1.1 p=0.095 |
FC=0.9 p=0.136 |
FC=0.9 p=0.153 |
FC=1.2 p=0.074 |
FC=0.9 p=0.286 |
FC=0.8 p=0.084 |
FC=1 p=0.753 |
FC=0.9 p=0.101 |
FC=1.2 p=0.374 |
FC=0.8 p=0.006$ FC=0.5 p=0.003* |
FC=0.7-1 p=0.124-1 |
FC=0.3-0.8 p>0.024 |
FC=0.4-0.9 p>0.025 |
FC=0.7-1.1 p>0.062 |
| Angiogenin | FC=4 p=0.658 |
FC=5 p=0.391 |
FC=3 p=0.582 | FC=2 p=0.513 |
FC=0.5 p=0.45 |
FC=0.6 p=0.014 |
FC=0.3 p=7E-05 | FC=2 p=0.575 |
FC=0.7 p=0.006 | FC=3 p=0.838 |
FC<0.1 p=0.463 |
FC=0.3 p=1E-05 |
FC=1.1 p=0.859 |
FC=0.6-3 p>0.031 |
FC=1-1.5 p>0.4 |
FC=1.7-31 p>0.018 |
FC=0.3-1.4 p>0.1 |
FC=9 p=0.0002 $ |
| VEGF | FC=2 p=0.007 | FC=2 p=0.003 | FC=1.9 p=0.056 |
FC=2 p=0.017 | FC=1.1 p=0.954 |
FC=1.2 p=0.097 |
FC=1 p=0.779 |
FC=1.1 p=0.959 | FC=0.8 p=0.182 |
FC=0.8 p=0.043 | FC=1.1 p=0.345 |
FC=0.7 p=0.101 |
FC=1.6 p=0.021 |
FC=0.8-1 p>0.1 |
FC=0.8 p>0.1 |
FC=0.3-1 p>0.08 |
FC=0.7-1.5 p>0.4 |
FC=0.7-1.3 p>0.2 |
| NLR | FC=5 p=10-9 |
FC=6 p=10-9 |
FC=5 p=2x10-7 |
FC=4 p=4x10-7 | FC=0.7 p=0.001 |
FC=0.7 p=0.019 |
FC=0.6 p=2x10-5 |
FC=0.9 p=0.388 |
FC=1.5 p=0.721 |
FC=0.6 p=0.116 |
FC=0.9 p=0.465 |
FC=1.1 p=0.683 |
FC=1 p=0.594 |
FC=0.8 p=0.024* |
FC=0.5-0.9 p>0.1 |
FC=0.5 p=0.029* FC=0.6 p=0.022# |
FC=0.6-1.4 p=0.2-1 |
FC=0.6-1.1 p>0.1 |
IL, interleukin; IFN-γ, interferon gamma; TNF, tumour necrosis factor; ICAM-1, intercellular adhesion molecule 1; IP-10, interferon-gamma induced protein 10; VEGF, vascular endothelial growth factor; sCD40L, soluble CD40 ligand; G-CSF, granulocyte-colony stimulating factor; CCL5, CC motif chemokine ligand 5; TNF-RI, soluble TNF-receptor I; ICT, immunochemotherapy; 1L-IO, patients receiving PD-(L)1 inhibitors as monotherapy in the first line; ctrl, age-matched healthy controls; 2+L-IO, patients receiving PD-(L)1 inhibitors as monotherapy in the second-or-subsequent lines; BL, baseline; C1, sample after 1 cycle of treatment; C4, sample after 4 cycles of treatment; FC, fold change; NLR, neutrophil-to-lymphocyte ratio; $, for the ICT subgroup; *, for the 1L-IO subgroup; #,for the 2+L-IO subgroup; for detailed results please see Supplementary Table 4 .
Non-parametric statistical comparisons (please see Methods). Comparisons significant after B-H correction (FDR <0.1) are highlighted in green. Results with p<0.05, but FDR >0.1 are highlighted in grey.
1for the group sizes please see Figure 1 .