Table 3.

Relationship between pretreatment microenvironmental parameters in the tumor specimen obtained closest to treatment initiation, and clinical response to anti–PD-1a

Objective responsebClinical benefitc
Pathologic parameter (number of patients analyzed)All patientsn (%)Non (%)Yesn (%)P valuedNon (%)Yesn (%)P valued
Tumor PD-L1 expression (n = 41)e
 Absent18 (44)17 (94)1 (6)0.02517 (94)1 (6)0.005
 Present23 (56)14 (61)9 (39)12 (52)11 (48)
Immune cell infiltrate PD-L1 expression (n = 41)e
 Absent18 (44)16 (89)2 (11)0.14216 (89)2 (11)0.038
 Present23 (56)15 (65)8 (35)13 (57)10 (43)
Immune infiltrate score (n = 41)f
 Absent9 (22)8 (89)1 (11)0.4108 (89)1 (11)0.240
 Present32 (78)23 (72)9 (28)21 (66)11 (34)
TIL PD-1 expression (n = 37)g
 Absent21 (57)18 (86)3 (14)0.06717 (81)4 (19)0.077
 Present16 (43)9 (56)7 (44)8 (50)8 (50)
Immune cell or tumor cell PD-L2 expression (n = 13)e
 Absent9 (69)7 (78)2 (22)1.0006 (67)3 (33)0.497
 Present4 (31)4 (100)0 (0)4 (100)0 (0)
CD4:CD8 (n = 29)
 CD4 ≥ CD813 (45)10 (77)3 (23)0.4549 (69)4 (31)0.702
 CD4 < CD816 (55)10 (63)6 (37)9 (56)7 (44)
CD20+ B cells (n = 30)
 Absent19 (63)16 (84)3 (16)1.00016 (84)3 (16)0.372
 Presentf11 (37)9 (82)2 (18)7 (64)4 (36)
Lymphoid aggregates (n = 41)
 Absent35 (85)26 (74)9 (26)1.00025 (71)10 (29)1.000
 Present6 (15)5 (83)1 (17)4 (67)2 (33)
Necrosis (n = 41)
 Absent27 (66)19 (70)8 (30)0.44719 (70)8 (30)1.000
 Present14 (34)12 (86)2 (14)10 (71)4 (29)
Small sample (n = 41)
 No27 (66)20 (74)7 (26)1.00018 (67)9 (33)0.494
 Yes14 (34)11 (79)3 (21)11 (79)3 (21)
Interval between specimen procurement and treatment initiation (n = 41)
 <1 year16 (39)10 (63)6 (37)0.159 (56)7 (44)0.16
 ≥1 year25 (61)21 (84)4 (16)20 (80)5 (20)
  • aCorrelation of tumor cell PD-L1 expression with objective response was previously reported for 34 of 41 patients included in this series, using the “highest ever” value in the case of multiple specimens from individual patients (16).

  • bObjective response is defined as complete or partial tumor regression, RECIST 1.0 with modifications.

  • cClinical benefit is defined as objective response or stable disease lasting ≥6 months.

  • dFisher exact test, comparing responders with nonresponders for the pathologic parameter analyzed.

  • eTumor or infiltrating immune cells were considered PD-L1 or PD-L2 (+) if ≥5% of cells had membranous (cell surface) expression detected by IHC.

  • fImmune infiltrates (lymphocytes and histiocytes) and CD20+TIL were graded as “none,” “focal,” “moderate,” or “severe” (see Materials and Methods). TIL or CD20 “present” indicates grades “focal,” “moderate,” and “severe.”

  • gAbsent TIL PD-1 expression includes both cases where there were no TILs, and cases where TILs were present, but did not express PD-1.