Table 3.
Association between immune markers and progression-free survival among patients who received anti-PD-1/PD-L1 based regimens (N = 39).
| Immune phenotypes | Incidence of High/Very high (%) | Median PFS time (Very high/High vs. Moderate/Low/Very low biomarker expression *) (Months) |
P-value ** |
|---|---|---|---|
| Checkpoint markers | |||
| PD-1 | 1 (2.6%) | 2.4 vs 4.4 | 0.423 |
| PD-L1 | 3 (7.7%) | 4.4 vs 2.7 | 0.335 |
| PD-L2 | 6 (15.4%) | 2.0 vs 5.9 | 0.229 |
| Other Checkpoint markers | |||
| BTLA | 0 (0.0%) | - vs 4.4 | - |
| CTLA-4 | 2 (5.1%) | 4.4 vs 2.9 | 0.522 |
| LAG3 | 3 (7.7%) | 4.4 vs 2.9 | 0.638 |
| TIM3 | 6 (15.4%) | 1.7 vs 5.9 | 0.007 *** |
| VISTA | 5 (12.8%) | 1.7 vs 5.9 | 0.001 *** |
| TNFRSF14 | 0 (0.0%) | - vs 4.4 | - |
| Macrophage-associated markers | |||
| CCL2 | 8 (20.5%) | 2.4 vs 5.9 | 0.096 |
| CCR2 | 6 (15.4%) | 1.7 vs 4.9 | 0.950 |
| CD163 | 10 (25.6%) | 2.7 vs 4.9 | 0.180 |
| CD68 | 5 (12.8%) | 1.7 vs 5.9 | 0.009 *** |
| CSF1R | 11 (28.2%) | 2.4 vs 5.9 | 0.127 |
| Metabolic immune escape markers | |||
| ADORA2A | 3 (7.7%) | - vs 2.9 | 0.188 |
| CD39 | 7 (17.9%) | 2.7 vs 5.9 | 0.176 |
| IDO1 | 4 (10.3%) | 4.4 vs 2.9 | 0.911 |
| Anti-inflammatory response markers | |||
| IL10 | 8 (20.5%) | 2.0 vs 5.9 | 0.144 |
| TGFB1 | 6 (15.4%) | 1.7 vs 4.9 | 0.496 |
| T-cell primed markers | |||
| CD137 | 4 (10.3%) | 4.4 vs 2.9 | 0.984 |
| CD27 | 1 (2.6%) | 2.4 vs 4.4 | 0.423 |
| CD28 | 4 (10.3%) | 1.7 vs 4.9 | 0.018 |
| CD40 | 2 (5.1%) | 2.0 vs 4.4 | 0.726 |
| CD40 ligand | 1 (2.6%) | 2.0 vs 4.4 | 0.271 |
| GITR | 6 (15.4%) | 15.5 vs 2.9 | 0.268 |
| ICOS | 3 (7.7%) | - vs 2.7 | 0.320 |
| ICOS ligand | 9 (23.1%) | 2.7 vs 4.4 | 0.765 |
| OX40 | 3 (7.7%) | 20.6 vs 2.7 | 0.092 |
| OX40 ligand | 9 (23.1%) | 2.4 vs 5.9 | 0.061 |
| GZMB | 5 (12.8%) | 4.4 vs 2.9 | 0.740 |
| IFNG | 2 (5.1%) | 4.4 vs 2.9 | 0.748 |
| CD80 (B7-1) | 7 (17.9%) | 4.4 vs 2.9 | 0.638 |
| CD86 (B7-2) | 8 (20.5%) | 2.0 vs 5.9 | 0.030 |
| TBX21 | 2 (5.1%) | 0.8 vs 4.9 | 0.156 |
| Pro-inflammatory response markers | |||
| IL1B | 15 (38.5%) | 2.7 vs 4.9 | 0.884 |
| STAT1 | 3 (15.4%) | 6.3 vs 2.7 | 0.963 |
| TNF | 5 (12.8%) | 1.1 vs 4.4 | 0.337 |
| DDX58 | 12 (30.8%) | 4.4 vs 2.9 | 0.686 |
| MX1 | 8 (20.5%) | 4.4 vs 2.9 | 0.581 |
| CXCL10 | 4 (10.3%) | 4.4 vs 2.9 | 0.814 |
| CXCR6 | 6 (15.4%) | 4.4 vs 2.9 | 0.864 |
| Tumor infiltrating lymphocytes markers | |||
| CD2 | 3 (15.4%) | NR vs 2.7 | 0.320 |
| CD3 | 0 (0.0%) | - vs 4.4 | - |
| CD4 | 9 (23.1%) | 2.4 vs 5.9 | 0.141 |
| CD8 | 2 (5.1%) | 0.9 vs 4.9 | 0.009 |
| FOXP3 | 8 (20.5%) | 4.4 vs 2.9 | 0.449 |
| KLRD1 | 5 (12.8%) | 2.0 vs 4.9 | 0.142 |
| SLAMF4 | 4 (10.3%) | 2.0 vs 4.9 | 0.257 |
| CD20 | 1 (2.6%) | 2.4 vs 4.4 | 0.423 |
| Other immunotherapy markers | |||
| CD38 | 6 (15.4%) | 4.4 vs 2.9 | 0.605 |
| GATA3 | 5 (12.8%) | 5.9 vs 2.9 | 0.503 |
Abbreviation: HR, hazard ratio; PFS, progression-free survival; NR, not reached.
All patient received anti-PD-1/PD-L1 based therapy (alone or in combination with other agent).
*See Methods for definition of very high, high, moderate, low, very low biomarker expression.
**P-values with univariate analysis by log-rank test.
***P-values significant after the Bonferroni correction. Cutoff for significant P-values were defined as 0.05/number of markers at each section. For example, there were 6 variables in “Other Checkpoint markers”. For this category, significant P-values were defined as less than or equal to 0.0083 (0.05/6).