Table 4.
Effect of immune markers on pathologic response in the total area, tumor sample, and tumor microenvironment of surgical specimens (no 18F-FDG-PET/CT)
| Post-CRT author | Assessment | Cut-off value | Sample size | n pGR (TRG1–2)† | n pPR (TRG3–5)† | Correlation biomarkers with PR in surgical specimens | p-Value total area | p-Value tumor | p-Value TME |
|---|---|---|---|---|---|---|---|---|---|
| CD8 | |||||||||
| Fassan et al., 201944 a,b | Cell count/5 HPF | Median | 88 | 23 | 65 | pGR had significant enrichment of CD8+ compared with pPR | <0.001 | NA | NA |
| Goedegebuure et al., 202124 a | Cell count/mm2 | Median | 40 | 12 (TRG1) | 28 (TRG2–5) | TRG1 was significantly more present in a CD8-dominant infiltrate | 0.027 | NA | NA |
| Haddad et al., 202246 c | % ± SD | Mean | 17 | 11 | 6 | Significant enrichment of CD8+ in pGR compared with pPR | NA | <0.001 | 0.001 |
| Koemans et al., 202130 c | Cell count/mm2 | 4 hotspots of 0.5 mm*0.5mm2 | 123 | 62 | 61 | pGR had significantly less CD8+ compared with pPR | 0.001 | NA | NA |
| Kotsafti et al., 202126 a,b | Cell count/5 HPF | Median | 123 | 20 | 103 | Peritumoral healthy mucosa in pGR had significant high CD8+ compared with pPR | 0.05 | NA | NA |
| Soeratram et al., 202127 a | Cells/mm2 | Mean and median | 89 | 55 (TRG1–3) | 25 (TRG4–5) | Higher CD8 in the tumor epithelium was associated with pPR; higher CD8 in tumor stroma was associated with pGR | NA | 0.000 | 0.000 |
| CD4 | |||||||||
| Fassan et al., 202244 a,b | Cell count/5 HPF | Median | 88 | 23 | 65 | pGR had significant enrichment of CD4+ compared with pPR | 0.006 | NA | NA |
| Haddad et al., 202246 c | % ± SD | Mean | 28 | 13 | 15 | pGR had significant enrichment of CD4+ compared with pPR | NA | 0.009 | 0.004 |
| Koemans et al., 202130 c | Cell count/mm2 | 4 hotspots of 0.5 mm*0.5mm2 | 123 | 62 | 61 | pGR had significantly less CD4+ compared with pPR | <0.001 | NA | NA |
| CD3 | |||||||||
| Haddad et al., 202246 c | % ± SD | Mean | 88 | 13 | 15 | pGR had significant enrichment of CD3+ compared with pPR | NA | <0.001 | <0.001 |
| Koemans et al., 202130 c | Cell count/mm2 | 4 hotspots of 0.5 mm*0.5mm2 | 123 | 62 | 61 | pGR had significant less CD3+ compared with pPR | <0.001 | NA | NA |
| CD80 | |||||||||
| Fassan et al., 202244 a,b | Cell count/5 HPF | Median | 88 | 23 | 65 | No difference between pGR and pPR | 0.4874 | NA | NA |
| Kotsafti et al., 202126 a,b | Cell count/5 HPF | Median | 123 | 20 | 103 | No difference between pGR and pPR | 0.89 | NA | NA |
| PD-1 | |||||||||
| Kotsafti et al., 202126 a,b | NA | – | 123 | 20 | 103 | pGR had significantly lower mRNA PD-1 compared with pPR | 0.0065 | NA | NA |
| PD-L1 | |||||||||
| Fassan et al., 201944 a,b | Cell count/5 HPF | – | 88 | 23 | 65 | pGR had significant levels of PD-L1 expressions either on tumor cells or in lymphocytes than pPR | NA | 0.004 | NA |
| Huang et al., 201925 d | >1% = positive, <1 = negative | – | 107 | 28 | 79 | Positive tumoral PD-L1 expression was significantly associated with pPR | NA | 0.036 | NA |
| Koemans et al., 202130 c | 0%, 1–5%, 6–9%, 10–29%, >30% | – | 123 | 62 | 61 | No association between PD-L1 positivity in tumor cells and PR; pPR had significantly more PD-L1-positive lymphocytes | NA | 1.00 | 0.001 |
| Kotsafti et al., 202126 a,b | NA | – | 123 | 20 | 103 | pGR had significantly lower mRNA PD-L1 compared with pPR | 0.0005 | NA | NA |
| Soeratram et al., 202127 a | <1–4%, 5–24%, 25–100% | Mean and median | 89 | 55 (TRG1–3) | 25 (TRG4–5) | CPS > 1 was associated with pPR | 0.010 | NA | NA |
Bold values indicate the significant values (p < 0.05)
a Pearson’s Chi-square test
b Two-tailed z-test
c Mann–Whitney U-test
d Logistic regression
18F-FDG-PET/CT F-18 fluorodeoxyglucose positron emission tomography/computed tomography, TRG tumor regression grade, pGR pathologic good responders, pPR pathologic poor responders, PR pathologic response, CRT chemoradiotherapy, CPS combined positive score, TME tumor microenvironment, NA not available, PD-1 programmed death-1, PD-L1 programmed death-ligand 1, HPF high power field, SD standard deviation