Table 2.
Summary of the prognostic value of TILs obtained from the subgroup analysis including dense TIL’s assessment, Deadline, Variable, Location of TILs, Cutoff of TILs, Therapeutic approach, Pathology and subsets of TILs
| Subgroup | Number of studies | Number of participants | Random-effects model | Fixed-effects model | Heterogeneity | |||
|---|---|---|---|---|---|---|---|---|
| HR (95%CI) | P | HR (95%CI) | P | I2 | Ph | |||
| Dense TIL’s assessment | 14 | 4843 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0.001 | 78.30% | 0 |
| percentage of stromal TILs | 11 | 3666 | 1.49 (1.11–1.99) | 0.008 | 1.45 (1.16–1.80) | 0 | 28.40% | 0.175 |
| number of touching TILs | 3 | 1177 | 4.73 (2.28–9.80) | 0 | 5.1 (3.66–7.11) | 0 | 72.40% | 0.027 |
| Outcome | 14 | 4843 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| ipsilateral recurrence | 12 | 4149 | 2.26 (1.31–3.91) | 0.004 | 2.33 (1.89–2.88) | 0 | 80.60% | 0 |
| all kinds of recurrence | 2 | 694 | 1.61 (1.11–2.33) | 0.011 | 1.61 (1.11–2.33) | 0.011 | 0 | 0.662 |
| Variable | 14 | 4335 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| univariate analysis | 5 | 1307 | 1.42 (1.02–1.99) | 0.039 | 1.42 (1.02–1.99) | 0.039 | 0.00% | 0.42 |
| multivariate analysis | 9 | 3028 | 2.30 (1.27–4.17) | 0.006 | 2.52 (2.03–3.14) | 0 | 83.40% | 0 |
| Location of TILs | 14 | 4843 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| touching TILs | 2 | 204 | 6.04 (2.64–13.81) | 0 | 6.04 (2.64–13.81) | 0 | 0 | 0.958 |
| stromal TILs | 12 | 4639 | 1.81 (1.13–2.90) | 0.013 | 2.02 (1.67–2.43) | 0 | 79.40% | 0 |
| Cutoff of TILs | 14 | 5366 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| 1–5% | 6 | 2625 | 1.24 (0.90–1.70) | 0.186 | 1.24 (0.90–1.70) | 0.186 | 0 | 0.933 |
| 6–30% | 2 | 664 | 1.73 (1.17–2.56) | 0.006 | 1.73 (1.17–2.56) | 0.006 | 0 | 0.69 |
| 31–50% | 3 | 900 | 3.03 (0.71–12.97) | 0.134 | 1.57 (0.97–2.56) | 0.068 | 81.20% | 0.005 |
| counts (5 or 15 or 20) | 3 | 1177 | 4.73 (2.28–9.80) | 0 | 5.10 (3.66–7.11) | 0 | 72.40% | 0.027 |
| Therapeutic approach | 14 | 4869 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| breast conserving therapy or mastectomy | 5 | 1690 | 2.77 (1.26–6.07) | 0.011 | 2.51 (1.99–3.17) | 0 | 89.50% | 0 |
| breast conserving therapy + radiotherapy | 4 | 1315 | 2.26 (1.29–3.95) | 0.004 | 2.24 (1.49–3.35) | 0 | 42.10% | 0.159 |
|
surgery + adjuvant therapies (hormonal therapy, radiotherapy) |
5 | 1864 | 1.16 (0.62–2.18) | 0.645 | 1.07 (0.69–1.68) | 0.753 | 28.30% | 0.233 |
| Pathology | 14 | 4843 | 2.11 (1.35–3.28) | 0.001 | 2.13 (1.77–2.55) | 0 | 78.30% | 0 |
| pure DCIS | 9 | 2995 | 2.37 (1.31–4.28) | 0.004 | 2.54 (2.02–3.18) | 0 | 81.90% | 0 |
| pure DCIS & pure DCIS mixed with microinvasive or invasive breast cancer | 2 | 162 | 5.03 (1.63–15.52) | 0.005 | 5.09 (1.71–15.13) | 0.003 | 1.60% | 0.313 |
| DCIS | 3 | 1686 | 1.32 (0.88–1.97) | 0.184 | 1.36 (0.98–1.89) | 0.064 | 22.60% | 0.275 |
| subset of TILs | 10 | 2190 | 2.29 (1.31–3.99) | 0.003 | 2.55 (2.06–3.16) | 0 | 77.80% | 0 |
| CD4+ TILs | 2 | 601 | 1.98 (1.14–3.44) | 0.015 | 1.97 (1.31–2.96) | 0.001 | 45.80% | 0.174 |
| CD8+ TILs | 1 | 402 | 0.90 (0.47–1.71) | 0.747 | 0.90 (0.47–1.71) | 0.747 | 0.00% | – |
| FOXP3+ TILs | 2 | 468 | 1.83 (1.23–2.70) | 0.003 | 1.83 (1.23–2.70) | 0.003 | 0.00% | 0.382 |
| PD-L1+ TILs | 5 | 719 | 6.21 (4.26–9.06) | 0 | 6.21 (4.26–9.06) | 0 | 0.00% | 0.708 |