Table 1.
Univariate and multivariate analysis of CTLA-4 clinical and immunomic features and transcriptomic expression (N = 514 patients).
| Feature* | Number of patients with ‘High’ CTLA-4$
(N (%)) |
Odds ratio (OR) for ‘High’ CTLA-4 (95% CI) | Univariate p-value | Multivariate OR for ‘High’ CTLA-4 (95% CI) ‡ | Multivariate p-value |
|---|---|---|---|---|---|
| Age ⩾ 61 years (n = 256) Age < 61 years (n = 258) |
45 (18%) 42 (16%) |
1.1 (0.7–1.7) 0.9 (0.9–1.4) |
p = 0.7 | ||
| Men (N = 204) Women (N = 310) |
32 (16%) 55 (18%) |
0.9 (0.5–1.4) 1.2 (0.7–1.9) |
p = 0.5 | ||
| ‘High’ PD-L1 (n = 67) ‘Low/Moderate’ PD-L1 (n = 447) |
29 (43%) 58 (13%) |
5.1 (2.9–8.9) 0.2 (0.1–0.3) | p < 0.0001 | 1.2 (0.5–2.7) 0.8 (0.4–0.8) |
p = 0.7 |
| ‘High’ PD-1 (n = 93) ‘Low/Moderate’ PD-1 (n = 421) |
54 (58%) 33 (8%) |
16.3 (9.4–28.0) 0.1 (0.03–0.1) |
p < 0.0001 | 9.7 (5.2–18.0) 0.2 (0.1–0.3) |
p < 0.0001 (‘High’ CTLA-4 found more frequently with ‘High’ PD-1) |
| ‘High’ PD-L2 (n = 100) ‘Low/Moderate’ PD-L2 (n = 414) |
40 (40%) 47 (11%) |
5.2 (3.2–8.6) 0.2 (0.1–0.3) | p < 0.0001 | 2.3 (1.2–4.5) 0.4 (0.2–0.9) |
p = 0.02 (‘High’ CTLA-4 found more frequently with ‘High’ PD-L2) |
| ‘High’ LAG-3 (n = 116) ‘Low/Moderate’ LAG-4 (n = 398) |
47 (41%) 40 (10%) |
6.1 (3.7–10.0) 0.2 (0.1–0.3) | p < 0.0001 | 2.0 (1.1–3.9) 0.5 (0.3–0.9) |
p = 0.04 (‘High’ CTLA-4 found more frequently with ‘High’ LAG-3) |
| TMB ⩾ 10 mutations/mb (n = 33) TMB < 10 mutations/mb (n = 417) |
5 (15%) 63 (15%) |
1.0 (0.4–2.7) 1.0 (0.4–2.7) |
p = 1.0 | ||
| Colorectal cancer (n = 140) Other cancers (n = 374) |
20 (14%) 67 (18%) |
0.8 (0.4–1.3) 1.3 (0.8–2.3) |
p = 0.3 | ||
| Breast cancer (n = 49) Other cancers (n = 465) |
11 (22%) 76 (16%) |
1.5 (0.7–3.0) 0.7(0.3–1.4) |
p = 0.3 | ||
| Ovarian cancer (n = 43) Other cancers (n = 471) |
4 (9%) 83 (18%) |
0.5 (0.2–1.4) 2.1 (0.7–6.0) |
p = 0.1 | ||
| Cervical cancer (n = 5) Other cancers (n = 509) |
4 (80%) 83 (16%) |
20.5 (2.3–186.0) 0.04 (0.0–0.4) |
p = 0.002 | 32.7 (2.9–370.2) 0.03 (0.003–0.3) |
p = 0.005 (‘High’ CTLA-4 found more frequently with cervical cancer) |
| Pancreatic cancer (n = 55) Other cancers (n = 459) |
13 (24%) 74 (16%) |
1.6 (0.8–3.1) 0.6 (0.3–1.8) |
p = 0.2 | ||
| Uterine cancer (n = 24) Other cancers (n = 490) |
3 (13%) 84 (17%) |
0.7 (0.2–2.4) 1.4(0.4–5.0) |
p = 0.5 | ||
| Neuroendocrine cancer (n = 15) Other cancers (n = 499) |
2 (13%) 85 (17%) |
0.7 (0.2–3.4) 1.3 (0.3–6.0) |
p = 0.7 | ||
| Lung cancer (n = 20) Other cancers (n = 494) |
4 (20%) 83 (17%) |
1.2 (0.4–3.8) 0.8 (0.3–2.5) |
p = 0.7 | ||
| Sarcoma (n = 24) Other cancers (n = 490) |
3 (13%) 84 (17%) |
0.7 (0.2–2.4) 1.4 (0.4–5.0) |
p = 0.5 | ||
| Melanoma (n = 6) Other cancers (n = 508) |
2 (33%) 85 (17%) |
2.5 (0.4–13.8) 0.4 (0.1–2.2) |
p = 0.3 |
*
Data for some variables such as TMB was not available for all patients, so the total number of patients in some categories is lower. Only 15 patients had microsatellite instability and thus microsatellite status was not calculated.
$
High LAG-3 or PD-L1 or PD-1 or PD-L2 or CTLA-4 refers to ⩾75 transcript expression percentile rank; ‘Low/Moderate’ LAG-3 or PD-L1 or PD-1 or PD-L2 or CTLA-4 refers to <75 percentile rank transcript expression.
‡
Variables with p value ⩽ 0.05 were used for multivariate analysis and p values are bolded to indicate significance.