Table 2.

Comparison of patients’ clinical characteristics between the T-cell activation-related plasma protein (22 proteins) signature (immune “hot” vs. immune “cold”) subgroups. p-values were obtained using Fisher’s exact, Mann-Whitney, or chi-square test.

Clinical Characteristic	Immune “Hot”	Immune “Cold”	p-Value
	Protein Signature	Protein Signature
	n = 24 (55.8%)	n = 19 (44.2%)
Sex			0.03
Female	9 (37.5)	14 (73.7)
Male	15 (62.5)	5 (26.3)
Median age (years; at the start of immunotherapy)	74.5	68.0	0.005
Smoking status (at diagnosis)			>0.999
Ever smoker (smoker/ex-smoker)	22 (91.7)	17 (89.5)
Never smoker	2 (8.3)	2 (10.5)
Tumor type			0.674
Adenocarcinoma	15 (62.5)	12 (63.2)
Squamous cell carcinoma	8 (33.3)	5 (26.3)
Other	1 (4.2)	2 (10.5)
Stage			0.752
III	6 (31.6)	10 (41.7)
IV	13 (68.4)	14 (58.3)
Performance status			0.203
0 1 2	4 (16.7) 15 (62.5) 5 (20.8)	7 (36.8) 7 (36.8) 5 (26.3)
PD-L1			0.197
No expression	0 (0.0)	0 (0.0)
<1%	3 (12.5)	7 (36.8)
1–49% 50–100%	6 (25.0) 11 (45.8)	4 (21.1) 6 (31.6)
N/A	4 (15.8)	2 (10.5)
Therapeutic agent			0.643
Atezolizumab	3 (12.5)	4 (21.1)
Durvalumab	1 (4.2)	0 (0.0)
Nivolumab	6 (25.0)	6 (31.6)
Pembrolizumab	14 (58.3)	9 (47.4)
Therapy line at which immunotherapy was initiated			0.246
1st line	10 (41.7)	3 (15.8)
2nd line	9 (37.5)	10 (52.6)
3rd line	4 (16.7)	5 (26.3)
4th line	1 (4.2)	0 (0.0)
5th line	0 (0.0)	1 (5.3)
Response			0.065
Progressive disease (PD)	6 (25.0)	12 (63.2)
Stable disease (SD)	5 (20.8)	1 (5.3)
Partial response (PR)	7 (29.2)	4 (21.1)
Complete remission (CR)	0 (0.0)	0 (0.0)
N/A	6 (33.3)	2 (10.5)
Clinical benefit (SD, PR, CR) progressive disease (PD) N/A	12 (50.0) 6 (25.0) 6 (25.0)	4 (21.1) 12 (63.2) 3 (15.8)	0.020
Survival (from the start of immunotherapy)
Median overall survival (days) ± SD	402.5 ± 213.0	236.0 ± 178.8	-
Median progression-free survival (days) ± SD	106.0 ± 125.9	98.5 ± 56.0	-

N/A, not applicable.