Table 1. Significant factors in univariate cox regression of OS and RFS.
| Factors | OS | RFS | |||||||
|---|---|---|---|---|---|---|---|---|---|
| No | HR | 95% CI | P value | No | HR | 95% CI | P value | ||
| Distance between positive TILs (one positive TIL to another TIL) | |||||||||
| PD-1 | |||||||||
| Near (≤125.34 px) | 27 | 1.000 | |||||||
| Far (>125.34 px) | 74 | 1.975 | 1.078–3.618 | 0.028 | |||||
| OX40L | |||||||||
| Near (≤48.14 px for OS, ≤61.55 px for RFS) | 92 | 1.000 | 98 | 1.000 | |||||
| Far (>48.14 px for OS, >61.55 px for RFS) | 23 | 1.788 | 1.076–2.989 | 0.025 | 17 | 1.801 | 1.032–3.144 | 0.038 | |
| OX40 | |||||||||
| Near (≤98.33 px) | 92 | 1.000 | |||||||
| Far (>98.33 px) | 26 | 1.752 | 1.078–2.846 | 0.024 | |||||
| KIR-3D | |||||||||
| Near (≤13.44 px) | 13 | 1.000 | |||||||
| Far (>13.44 px) | 96 | 0.416 | 0.217–0.799 | 0.008 | |||||
| Distance between positive TCs (one positive TC to another positive TC) | |||||||||
| TIM-3 | |||||||||
| Near (≤546.86 px) | 59 | 1.000 | |||||||
| Far (>546.86 px) | 11 | 2.039 | 1.032–4.030 | 0.040 | |||||
| galectin9 | |||||||||
| Near (≤85.97 px for OS, ≤119.40 px for RFS) | 65 | 1.000 | 75 | 1.000 | |||||
| Far (>85.97 px for OS, >119.40 px for RFS) | 35 | 1.820 | 1.105–2.999 | 0.019 | 25 | 1.719 | 1.002–2.949 | 0.049 | |
| KIR-2D | |||||||||
| Near (≤24.22 px) | 68 | 1.000 | |||||||
| Far (>24.22 px) | 39 | 1.849 | 1.151–2.969 | 0.011 | |||||
| Distance between positive TCs and positive TIL (one positive TC to one positive TIL) | |||||||||
| OX40L | |||||||||
| Near (≤94.06 px) | 50 | 1.000 | 50 | 1.000 | |||||
| Far (>94.06 px) | 62 | 0.570 | 0.361–0.902 | 0.016 | 62 | 0.576 | 0.366–0.906 | 0.017 | |
| MHC-II | |||||||||
| Near (≤18.68 px) | 13 | 1.000 | |||||||
| Far (>18.68 px) | 97 | 0.374 | 0.200–0.699 | 0.002 | |||||
| KIR-3D | |||||||||
| Near (≤20.28 px) | 35 | 1.000 | 35 | 1.000 | |||||
| Far (>20.28 px) | 73 | 2.337 | 1.366–3.977 | 0.002 | 73 | 2.444 | 1.379–4.330 | 0.002 | |
| Distance between all TCs and all TILs (one TC to one TIL) | |||||||||
| Near (≤44.41 px) | 83 | 1.000 | |||||||
| Far (>44.41 px) | 38 | 1.672 | 1.069–2.614 | 0.024 | |||||
| Distance between all TCs and positive TILs (one TC to one positive TIL) | |||||||||
| OX40L | |||||||||
| Near (≤173.56 px) | 96 | 1.000 | |||||||
| Far (>173.56 px) | 20 | 1.731 | 1.025–2.922 | 0.040 | |||||
| OX40 | |||||||||
| Near (≤445.89 px) | 104 | 1.000 | |||||||
| Far (>445.89 px) | 14 | 1.777 | 0.991–3.187 | 0.054 | |||||
| MHC-II | |||||||||
| Near (≤44.03 px for OS, ≤135.56 px for RFS) | 49 | 1.000 | 96 | 1.000 | |||||
| Far (>44.03 px for OS, >135.56 px for RFS) | 63 | 1.415 | 0.915–2.299 | 0.113 | 16 | 1.761 | 0.984–3.150 | 0.057 | |
| KIR-2D | |||||||||
| Near (≤223.71 px) | 93 | 1.000 | |||||||
| Far (>223.71 px) | 16 | 1.833 | 1.031–3.258 | 0.039 | |||||
| KIR-3D | |||||||||
| Near (≤21.19 px) | 35 | 1.000 | 35 | 1.000 | |||||
| Far (>21.19 px) | 74 | 2.235 | 1.208–3.901 | 0.005 | 74 | 2.017 | 1.181–3.443 | 0.010 | |
| Percentage of positive TILs | |||||||||
| OX40 | |||||||||
| Low (≤44% for OS, ≤52% for RFS) | 84 | 1.000 | 95 | 1.000 | |||||
| High (>44% for OS, >52% for RFS) | 24 | 1.739 | 1.087–2.781 | 0.026 | 23 | 2.015 | 1.201–3.383 | 0.008 | |
| galectin9 | |||||||||
| Low (≤23% for OS, ≤20% for RFS) | 22 | 1.000 | 20 | 1.000 | |||||
| High (>23% for OS, >20% for RFS) | 83 | 1.964 | 1.002–3.850 | 0.049 | 85 | 2.053 | 1.016–4.149 | 0.045 | |
| KIR-2D | |||||||||
| Low (≤37%) | 46 | 1.000 | |||||||
| High (>37%) | 83 | 0.593 | 0.373–0.944 | 0.028 | |||||
| KIR-3D | |||||||||
| Low (≤99% for OS, ≤85% for RFS) | 84 | 1.000 | 26 | 1.000 | |||||
| High (>99% for OS, >85% for RFS) | 25 | 0.327 | 0.128–0.836 | 0.020 | 83 | 0.327 | 0.128–0.833 | 0.019 | |
| Percentage of positive TCs | |||||||||
| MHC-II | |||||||||
| Low (≤93%) | 99 | 1.000 | |||||||
| High (>93%) | 13 | 0.425 | 0.185–0.979 | 0.044 | |||||
| galectin9 | |||||||||
| Low (≤41%) | 85 | 1.000 | |||||||
| High (>41%) | 20 | 0.450 | 0.223–0.909 | 0.026 | |||||
| KIR-3D | |||||||||
| Low (≤99%) | 95 | 1.000 | |||||||
| High (>99%) | 14 | 0.561 | 0.325–0.968 | 0.038 | |||||
| Clinical factors | |||||||||
| Surgery type | |||||||||
| Wedge | 2 | 1.000 | |||||||
| Segmentectomy | 3 | 9534.267 | 0–3.547E+56 | ||||||
| Lobectomy | 62 | 7210.961 | 0–2.663E+56 | ||||||
| Bilobectomy | 7 | 6049.498 | 0–2.242E+56 | ||||||
| Pneumonectomy | 41 | 14177.646 | 0–5.236E+56 | ||||||
| Sleeve lobectomy | 6 | 10961.091 | 0–4.059E+56 | 0.020 | |||||
| Pathology | |||||||||
| Adenocarcinoma | 38 | 1.000 | |||||||
| Non-adenocarcinoma | 85 | 1.678 | 1.004–2.806 | 0.048 | |||||
| T-stage | |||||||||
| 1 | 85 | 1.000 | 85 | 1.000 | |||||
| 2 | 36 | 2.011 | 1.260–3.210 | 0.003 | 36 | 2.011 | 1.260–3.210 | 0.003 | |
| N-stage | |||||||||
| 0 | 63 | 1.000 | 63 | 1.000 | |||||
| 1 | 58 | 2.479 | 1.586–3.873 | <0.0001 | 58 | 2.479 | 1.586–3.873 | <0.0001 | |
| M-stage | |||||||||
| 0 | 114 | 1.000 | 114 | 1.000 | |||||
| 1 | 7 | 4.019 | 1.803–8.961 | 0.001 | 7 | 3.855 | 1.734–8.574 | 0.001 | |
| Stage | |||||||||
| 1A | 80 | 1.000 | 80 | 1.000 | |||||
| 1B | 41 | 5.188 | 3.242–8.301 | <0.0001 | 41 | 4.092 | 2.574–6.504 | <0.0001 | |
No, number of each class; HR, hazard ratio; OS, overall survival; RFS, relapse-free survival; TC, tumor cell; TIL, tumor-infiltrating lymphocyte; KIR2D, killer cell immunoglobulin-like receptor-2D; KIR-3D, killer cell immunoglobulin-like receptor-3D; TIM-3, T cell immunoglobulin-3; LAG-3, lymphocyte activation gene-3; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand-1; MHC-II, major histocompatibility complex class II; OX40L, OX40-ligand. All cut-off points were determined by the X-Tile software.