Table 3.
Relationship of TIL PD-L1 expression to clinical and immune parameters in primary breast carcinomas
| TIL PD-L1 expressiona |
||||
|---|---|---|---|---|
| PD-L1neg (0,1) | PD-L1mod (2) | PD-L1diffuse (3) | P b | |
| Total evaluable tumors (n = 43) | 20 (47%) | 20 (47%) | 3 (7%) | |
| Tumor phenotype | .01* | |||
| Luminal | 8 (40%) | 5 (25%) | 1 (33%) | |
| HER-2+ | 2 (10%) | 11 (55%) | 1 (33%) | |
| Basal-like | 10 (50%) | 4 (20%) | 1 (33%) | |
| Median age (y, range) | 57 (34-79) | 51 (33-72) | 68 (57-88) | .57* |
| Patient race | .43 | |||
| Black | 9 (45%) | 6 (30%) | 0 | |
| White | 11 (55%) | 13 (65%) | 3 (100%) | |
| Other | 0 | 1 (5%) | 0 | |
| Tumor grade | .07 | |||
| 1 | 0 | 0 | 0 | |
| 2 | 9 (45%) | 3 (15%) | 0 | |
| 3 | 11 (55%) | 17 (85%) | 3 (100%) | |
| Median tumor size (cm, range) | 2.5 (1.2-12) | 2.3 (1.1-6) | 3.3 (2-4.5) | .10* |
| Multifocal disease | 3 (15%) | 5 (25%) | 0 | .84 |
| Stage | .91 | |||
| 1 | 4 (20%) | 5 (25%) | 0 | |
| 2 | 13 (65%) | 11 (55%) | 3 (100%) | |
| 3 | 3 (15%) | 4 (20%) | 0 | |
| Associated DCIS | n = 5 | n=5 | .17 | |
| PD-L1 negative | 5 (100%) | 2 (40%) | 0 | |
| PD-L1 positive | 0 | 3 (60%) | 0 | |
| TIL intensity scorec | .49 | |||
| 0 | 0 | 0 | 0 | |
| Focal: 1 | 5 (25%) | 2 (10%) | 0 | |
| Moderate: 2 | 10 (50%) | 9 (45%) | 1 (33%) | |
| Diffuse: 3 | 5 (25%) | 9 (45%) | 2 (67%) | |
| Carcinoma cell PD-L1 statusd | .04 | |||
| Carcinoma PD-L1+ | 1 (5%) | 7 (35%) | 1 (33%) | |
| Carcinoma PD-L1− | 19 (95%) | 13 (65%) | 2 (67%) | |
| Lymphoid aggregate score | .08 | |||
| 0 | 13 (65%) | 7 (35%) | 0 | |
| Focal: 1 | 2 (10%) | 7 (35%) | 1 (33%) | |
| Moderate: 2 | 1 (5%) | 1 (5%) | 1 (33%) | |
| Germinal centers: 3 | 4 (20%) | 5 (25%) | 1 (33%) | |
| Quantitative TIL count/mm2 | ||||
| Total CD3, median (range) | 732 (71-2294) | 1716 (435-8465) | 1871 (1653-2792) | .01* |
| Total CD4, median (range) | 711 (67-6369) | 2378 (405-13639) | 2526 (2422-2718) | .04* |
| Total CD8, median (range) | 806 (2-3169) | 1232 (175-3842) | 1053 (643-1386) | .32* |
| Total FoxP3, median (range) | 261 (64-1115) | 472 (87-1822) | 422 (289-425) | .25* |
| Total CD20, median (range) | 152 (6-1706) | 333 (28-5776) | 530 (58-596) | .08* |
| CD8/FoxP3 ratio, median (range) | 2 (0.8-7.9) | 2.2 (0.9-5.3) | 2.5 (2.2-3.3) | .67* |
| CD4/FoxP3 ratio, median (range) | 2.5 (0.86-11) | 4.8 (2.4-9.1) | 6.4 (5.98-8.4) | .14* |
Abbreviations: DCIS, ductal carcinoma in situ; HER-2, human epidermal growth factor receptor 2; TIL, tumor-infiltrating lymphocytes and macrophages.
The proportion of TILs expressing PD-L1 was graded as “none” (0), “focal” (1); “moderate” (2), or “severe” (3).
The P values of categorical variables are derived from Fisher exact test, and the P values of continuous variables are derived from 2-sided t tests. The P values with asterisk (*) indicate that P values are derived from comparison between the group PDL1 = 0/1 and group PDL1 = 2/3.
Immune infiltrates included TILs and accompanying histiocytes and were scored as “none” (0), “focal” (1), “moderate” (2), or “diffuse” (3); see “Materials and methods” section.
Tumor cells were considered PD-L1+ if greater than or equal to 5% of cells had membranous PD-L1 labeling.