PD-L1 expression

Tumor progression

PD-L1 positivity in tumor cells

Summary table
	No tumor progression (%)	Tumor progression (%)
Low PD-L1	53 (86.9)	8 (100)
High PD-L1	8 (13.1)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in tumor cells	5.7e-08 (NA, 5.4e+61)	0.99	1.3e-08 (0.00, Inf)	0.32

PD-L1 H-score in tumor cells

Summary table
	No tumor progression (%)	Tumor progression (%)
Low PD-L1	53 (86.9)	8 (100)
High PD-L1	8 (13.1)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 H-score in tumor cells	5.7e-08 (NA, 5.4e+61)	0.99	1.3e-08 (0.00, Inf)	0.32

PD-L1 positivity in stromal cells

Summary table
	No tumor progression (%)	Tumor progression (%)
Low PD-L1	35 (79.5)	6 (100)
High PD-L1	9 (20.5)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in stromal cells	5e-08 (NA, 3.9e+86)	0.99	1.2e-08 (0.00, Inf)	0.24

Overall mortality

PD-L1 positivity in tumor cells

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low PD-L1	50 (86.2)	12 (100)
High PD-L1	8 (13.8)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in tumor cells	3.6e-08 (NA, 5.2e+76)	0.99	1.3e-08 (0.00, Inf)	0.22

PD-L1 H-score in tumor cells

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low PD-L1	50 (86.2)	12 (100)
High PD-L1	8 (13.8)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 H-score in tumor cells	3.6e-08 (NA, 5.2e+76)	0.99	1.3e-08 (0.00, Inf)	0.22

PD-L1 positivity in stromal cells

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low PD-L1	34 (81)	7 (87.5)
High PD-L1	8 (19)	1 (12.5)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in stromal cells	0.61 (0.03, 4.16)	0.66	1.04 (0.13, 8.57)	0.97

Cancer-related mortality

PD-L1 positivity in tumor cells

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low PD-L1	60 (88.2)	2 (100)
High PD-L1	8 (11.8)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in tumor cells	9.5e-08 (NA, 2.4e+268)	1	3.7e-08 (0.00, Inf)	0.64

PD-L1 H-score in tumor cells

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low PD-L1	60 (88.2)	2 (100)
High PD-L1	8 (11.8)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 H-score in tumor cells	9.5e-08 (NA, 2.4e+268)	1	3.7e-08 (0.00, Inf)	0.64

PD-L1 positivity in stromal cells

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low PD-L1	39 (81.2)	2 (100)
High PD-L1	9 (18.8)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High PDL1 positivity in stromal cells	6.2e-08 (NA, 7e+250)	1	1.2e-08 (0.00, Inf)	0.46

FOXP3 expression

Tumor progression

FOXP3 positivity in intratumoral lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low FOXP3	32 (52.5)	4 (50)
High FOXP3	29 (47.5)	4 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High FOXP3 positivity in intratumoral lymphocytes	1.10 (0.24, 5.05)	0.9	0.97 (0.24, 3.89)	0.97

FOXP3 positivity in stromal lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low FOXP3	21 (65.6)	1 (25)
High FOXP3	11 (34.4)	3 (75)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High FOXP3 positivity in stromal lymphocytes	5.73 (0.65, 123.64)	0.15	3.92 (0.41, 37.91)	0.2

FOXP3 positivity in tumor cells

Summary table
	No tumor progression (%)	Tumor progression (%)
Low FOXP3	1 (100)	0 (NaN)
High FOXP3	0 (0)	0 (NaN)

Overall mortality

FOXP3 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low FOXP3	32 (55.2)	5 (41.7)
High FOXP3	26 (44.8)	7 (58.3)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High FOXP3 positivity in intratumoral lymphocytes	1.72 (0.49, 6.43)	0.4	1.31 (0.41, 4.13)	0.64

FOXP3 positivity in stromal lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low FOXP3	19 (59.4)	3 (75)
High FOXP3	13 (40.6)	1 (25)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High FOXP3 positivity in stromal lymphocytes	0.49 (0.023, 4.30)	0.55	0.42 (0.043, 4.03)	0.42

FOXP3 positivity in tumor cells

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low FOXP3	1 (100)	0 (NaN)
High FOXP3	0 (0)	0 (NaN)

Cancer-related mortality

FOXP3 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low FOXP3	36 (52.9)	1 (50)
High FOXP3	32 (47.1)	1 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High FOXP3 positivity in intratumoral lymphocytes	1.12 (0.043, 29.23)	0.93	0.88 (0.055, 14.13)	0.93

FOXP3 positivity in stromal lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low FOXP3	22 (61.1)	0 (NaN)
High FOXP3	14 (38.9)	0 (NaN)

FOXP3 positivity in tumor cells

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low FOXP3	1 (100)	0 (NaN)
High FOXP3	0 (0)	0 (NaN)

CD8 and Ki67 expression

Tumor progression

CD8 positivity in intratumoral lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low CD8	29 (47.5)	4 (50)
High CD8	32 (52.5)	4 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in intratumoral lymphocytes	0.91 (0.20, 4.15)	0.9	0.75 (0.19, 3.00)	0.68

CD8-Ki67 positivity in intratumoral lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low CD8-Ki67	43 (70.5)	6 (75)
High CD8-Ki67	18 (29.5)	2 (25)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8-Ki67 positivity in intratumoral lymphocytes	0.80 (0.11, 3.85)	0.79	0.77 (0.16, 3.84)	0.75

CD8 positivity in stromal lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low CD8	17 (56.7)	1 (20)
High CD8	13 (43.3)	4 (80)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in stromal lymphocytes	5.23 (0.67, 109.01)	0.16	5.57 (0.62, 50.14)	0.082

CD8-Ki67 positivity in stromal lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low CD8-Ki67	29 (100)	5 (100)
High CD8-Ki67	0 (0)	0 (0)

Ki67 positivity in intratumoral lymphocytes

Summary table
	No tumor progression (%)	Tumor progression (%)
Low Ki67	32 (54.2)	4 (50)
High Ki67	27 (45.8)	4 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High Ki67 positivity in intratumoral lymphocytes	1.19 (0.26, 5.45)	0.82	1.04 (0.26, 4.15)	0.96

Overall mortality

CD8 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low CD8	28 (48.3)	6 (50)
High CD8	30 (51.7)	6 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in intratumoral lymphocytes	0.93 (0.26, 3.31)	0.91	0.76 (0.24, 2.35)	0.63

CD8-Ki67 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low CD8-Ki67	39 (67.2)	11 (91.7)
High CD8-Ki67	19 (32.8)	1 (8.3)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8-Ki67 positivity in intratumoral lymphocytes	0.19 (0.0098, 1.07)	0.12	0.20 (0.025, 1.52)	0.051

CD8 positivity in stromal lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low CD8	15 (51.7)	3 (50)
High CD8	14 (48.3)	3 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in stromal lymphocytes	1.07 (0.17, 6.66)	0.94	1.39 (0.28, 6.93)	0.69

CD8-Ki67 positivity in stromal lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low CD8-Ki67	28 (100)	6 (100)
High CD8-Ki67	0 (0)	0 (0)

Ki67 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD (%)	DOC + DOD (%)
Low Ki67	29 (51.8)	8 (66.7)
High Ki67	27 (48.2)	4 (33.3)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High Ki67 positivity in intratumoral lymphocytes	0.54 (0.13, 1.91)	0.35	0.53 (0.16, 1.77)	0.29

Cancer-related

CD8 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low CD8	33 (48.5)	1 (50)
High CD8	35 (51.5)	1 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in intratumoral lymphocytes	0.94 (0.036, 24.50)	0.97	0.72 (0.045, 11.51)	0.82

CD8-Ki67 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low CD8-Ki67	48 (70.6)	2 (100)
High CD8-Ki67	20 (29.4)	0 (0)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8-Ki67 positivity in intratumoral lymphocytes	2.8e-08 (NA, 5e+278)	1	2.9e-09 (0.00, Inf)	0.21

CD8 positivity in stromal lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low CD8	18 (52.9)	0 (0)
High CD8	16 (47.1)	1 (100)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High CD8 positivity in stromal lymphocytes	5.3e+07 (0.00, NA)	1	1.9e+09 (0.00, Inf)	0.22

CD8-Ki67 positivity in stromal lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low CD8-Ki67	33 (100)	1 (100)
High CD8-Ki67	0 (0)	0 (0)

Ki67 positivity in intratumoral lymphocytes

Summary table
	ANOD + AWD + DOC (%)	DOD (%)
Low Ki67	36 (54.5)	1 (50)
High Ki67	30 (45.5)	1 (50)

Logistic and Cox’s proportional hazards regression models
Predictors	Odds Ratio (95% CI)	P value	Hazard Ratio (95% CI)	P value
High Ki67 positivity in intratumoral lymphocytes	1.20 (0.046, 31.21)	0.9	1.05 (0.066, 16.79)	0.97