Table 3.

Effect of immune markers on pathologic response in the total area, tumor sample, and tumor microenvironment of treatment-naïve biopsies (no ¹⁸F-FDG-PET/CT)

Pre-CRT	Author	Assessment	Cut-off value	Sample size	n pGR (TRG1–3)	n pPR (TRG4–5)	Correlation biomarkers with PR in biopsies	p-Value total area	p-Value tumor	p-Value TME
CD8
	Gobel et al., 202228 a,b	Cell count/mm2	Median	58	47	11	No significant difference in CD8 density between pGR and pPR	0.223	NA	NA
	Goedegebuure et al., 202124 a,b	Cell count/mm2	Median	40	31	9	High intratumoral density of CD8+ is associated with pGR No significant difference in stromal density between groups	NA	0.031	NM
	Soeratram et al., 202127 c	Cells/mm2	Mean and median	81	48	33	Higher combined mean density of CD8 was associated with pGR	0.001	0.013	0.026
PD-1
	Gobel et al., 202228 a,b	<1%, 1 to <10%, 10 to <50%, ≥50%	–	58	47	11	Intra- and peritumoral PD-1 had no significant influence on TRG	NA	NM	NM
	Soeratram et al., 202128 c	cells/mm2	Mean and median	81	48	33	pPR had significant higher stromal PD-1 in lymphocytes compared with pGR	NA	0.222	0.048
PD-L1
	Gobel et al., 202228  a,b	<1%, 1 to <10%, 10 to <50%, ≥50%	–	58	47	11	PD-L1-positive score in the tumoral area: no significant influence; PD-L1-positive score in the peritumoral area was found significantly more in pGR	NA	NM	0.036
	Soeratram et al., 202127  c	<1–4%, 5–24%, 25–100%	Mean and median	81	48	33	CPS > 1 was associated with lower TRG (1–3)	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

^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, PD-1 programmed death-1, PD-L1 programmed death-ligand 1, TME tumor microenvironment, NA not available, NM not mentioned