Table 1.
Summary of most important biomarkers that were studied for anti-CTLA-4 therapy and assessed risk of bias per article.
| Biomarker | N of Studies | N of Patients | Median Patients per Article (IQR) |
Response | PFS | OS | Quality Assessment |
|---|---|---|---|---|---|---|---|
| LDH | 20 | 2539 | 86 (53–86) | LDH was associated with response in 4/10 studies, not associated in 6/10 studies. | LDH was associated with PFS in 3/3 studies. | LDH was associated with OS in 12/16 studies, not associated in 4/16 studies. | 2/20 high risk, 14/20, moderate, 4/20 low risk of bias |
| NLR | 11 | 1632 | 78 (43–184) | NLR was associated with response in 3/5 studies, not associated in 2/5 studies. | NLR was associated with PFS in 4/5 studies, not associated in 1/5 studies. | NLR was associated with OS in 7/10 studies, not associated in 3/10 studies | 1/11 high risk, 6/11 moderate risk, 4/11 low risk of bias |
| TMB | 7 | 724 | 64 (56–174) | TMB was associated with response in 3/6 studies, not associated in 3/6 studies. | TMB was associated with OS in 2/4 studies, not associated in 2/4 studies. | 3/7 high risk, 4/7 moderate, 0/7 low risk of bias | |
| Neoantigen load (NAL) | 5 | 385 | 64 (54–107) | NAL was associated with response in 2/3 studies, not associated in 1/3 studies. | NAL was associated with OS in 2/2 studies. | 2/5 high risk 3/5 moderate, 0/5 low risk of bias | |
| PD-L1 expression on tumor cells | 5 | 637 | 111 (48–214) | PD-L1 was not associated with response in 5/5 studies. | PD-L1 was not associated with PFS in 1/1 studies. | PDL-1 was not associated with OS in 3/3 studies. | 2/5 high risk, 3/5 moderate, 0/5 low risk of bias |
| MDSCs | 4 | 726 | 48 (22–475) | MDSCs were associated with response in 3/3 studies. | MDSCs were associated with OS in 2/2 studies. | 1/4 high risk, 3/4 moderate risk, 0/3 low risk of bias | |
| T-cell inflamed GEP | 4 | 304 | 58 (33–192) | GEP was associated with response in 4/4 studies. | 2/4 high risk, 2/4 moderate, 0/4 low risk of bias | ||
| Tregs in tumor tissue | 4 | 169 | 38 (31–58) | Tregs were associated with response in 2/4 studies, not associated in 2/4 studies. | Tregs were associated with OS in 2/2 studies. | 0/4 high risk, 4/4 moderate, 0/4 low risk of bias | |
| monocytic MDSCs | 4 | 168 | 39 (32–55) | moMDSCs were associated with response in 2/2 studies. | moMDSCs were associated with PFS in 2/2 studies | moMDSCs were associated with OS in 1/1 studies. | 3/4 high risk 1/4 moderate risk, 0/4 low risk of bias |
| Tregs in blood | 3 | 741 | 95 (31–615) | Tregs were associated with response in 1/1 studies. | Tregs were associated with RFS in 1/1 studies | Tregs were associated with OS in 2/2 studies. | 1/3 high risk, 2/3 moderate risk, 0/3 as low risk of bias |
| CD8 memory T-cells in blood | 3 | 90 | 30 (17–43) | CD8 memory T-cells were associated with response in 2/2 studies. | CD8 memory T-cells were associated with OS in 3/3 studies. | 2/3 high risk, 1/3 moderate risk 0/1 low risk of bias | |
| TILs | 3 | 90 | 17 (9–64) | TILs were associated with response in 3/3 studies. | TILs were not associated with PFS in 1/1 studies. | TILs were not associated with OS in 1/1 studies. | 1/3 high risk, 2/3 moderate, 0/3 low risk of bias |
| TCR diversity in blood | 2 | 54 | 27 (N/A) | TCR diversity was associated with response in 2/2 studies. | TCR diversity was not associated with OS in 1/1 studies. | 1/2 high risk, 1/2 moderate risk, 0/2 low risk of bias | |
| NK cells in blood | 2 | 63 | 32 (N/A) | NK cells were associated with response in 1/2 studies, not associated in 1/2 studies. | 1/2 high risk, 1/2 moderate, risk 0/2 low risk of bias |
Abbreviations: GEP: gene expression profiling, IQR: interquartile range, LDH: lactate dehydrogenase, MDSCs: myeloid-derived suppressor cells, NK: natural killer, NLR: neutrophil-to-lymphocyte ratio, TCR: T-cell receptor, TILs: tumor-infiltrating lymphocytes, TMB: tumor mutation burden, Tregs: regulatory T cells.