1. PD-L1 expression patterns in the metastatic tumors to the lung: a comparative study with the primary non-small cell lung cancer
Zoran Gatalica1*, Jude Senarathne1, Semir Vranic2,3
 1 Caris Life Sciences, Phoenix, AZ, USA; 2 Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina; 3 School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Results
Table 1.
Abstract
Introduction: Immune check point inhibitors (anti-PD-1/PD-L1) therapy has revolutionized cancer treatment of several, advanced and chemotherapy resistant malignancies. PD-L1 expression on tumor (TC) and/or inflammatory cells (IC) has been associated with a more favorable therapy response. We compared PD-L1 distribution in a large cohort of advanced tumors metastatic to the lungs and compared it with the primary lung non-small cell carcinomas (NSCLC).
Materials and Methods: The study groups included 176 metastatic cancers and 81 NSCLC. Expression of PD-L1 was assessed using immunohistochemistry (SP142, Ventana). PD-L1 positivity was defined as 2+ intensity at ≥5% in TC or IC cells. All cases were further stratified into 4 categories based on the expression presence or absence of PD-L1 expression on tumor or IC cells. PD-L1 expression was correlated with total mutational load (TML) measured in tumors using Next-Generation Sequencing (NGS).
Results: Overall TC PD-L1 positivity was significantly higher in NSCLC compared with metastatic tumors (28% vs. 14%, p=0.009) although some metastatic cancers (e.g. triple-negative breast and head/neck carcinomas, melanoma) exhibited higher TC PD-L1 expression. In contrast, overall IC PD-L1 expression was predominantly observed in metastatic tumors (28% vs. 0%, p<0.001). The IC PD-L1 expression ranged from 0% for metastatic renal cell carcinomas to 36-38% in the metastatic breast and colon carcinomas and melanoma (Table 1). Consequently, the stratification based on PD-L1 distribution (TC vs. IC), resulted in significantly different patterns between the primary and metastatic tumors (p<0.001, Table 2). Mean TML (±SD) for NSCLC (10±5.6) differed significantly from metastatic carcinomas from other sites (6.6±2.7) (p=0.013) (Table 3).
Conclusion: Our study indicate that a substantial proportion of metastatic tumors to the lung exhibit PD-L1 expression on either tumor or inflammatory (immune) cells and are potentially amenable for the treatment with immune check point inhibitors.
Histotype
PD-L1 expression in
tumor cells
Total
[<5%]
[≥5%]
NSCLC
Adenocarcinoma
Squamous cell carcinoma
Other NSCLC
58 (72%)
44 (72%)
11 (73%)
3 (60%)
23 (28%)
17 (28%)
4 (27%)
2 (40%) 81 61 15 5
Metastatic carcinomas
Colorectal carcinoma
Gynecologic carcinomas
Breast carcinoma
Head and neck carcinomas
Pancreatic carcinoma
Renal cell carcinoma
113 (90%)
49 (96%)
21 (95%)
18 (86%)
9 (60%)
10 (100%)
6 (86%)
13 (10%)
2 (4%)
1 (5%)
3 (14%)
6 (40%)
0 (0%)
1 (14%)
126 51 22 21 10 7
Other metastatic tumors
Soft tissue tumors
Malignant melanoma
Other cancers
39 (78%)
12 (80%)
7 (64%)
20 (83%)
11 (22%)
3 (20%)
4 (36%)
4 (17%) 50 11 24
210 47
257
PD-L1 expression in inflammatory cells
[<1%]
[≥1%]
81 (100%)
61 (100%)
15 (100%)
5 (100%)
Breast carcinomas
87 (69%)
32 (63%)
16 (73%)
13 (62%)
7 (70%)
7 (100%)
39 (31%)
19 (37%)
6 (27%)
8 (38%)
3 (30%)
40 (81%)
13 (87%)
20 (80%)
10 (19%)
2 (13%)
4 (20%)
208 49
Histotype
TML category
Total
Low (≤6)
Intermediate (7-16)
High (≥17)
NSCLC (mean: 10.07, SD 5.608)
Metastatic carcinomas (mean: 6.60, SD 2.785)
Other metastatic tumors (mean 11.76, SD )
22 (29%)
49 (64%)*
5 (7%) 76
64 (60%)*
41 (39%)
1 (1%)
106
27 (57%)*
12 (26%)
8 (17%)** 47
113
102 14
229
Histotype
TME categories (PD-L1 expression)
Total
TC+/IC+
TC-/IC-
TC+/IC-*
TC-/IC+*
NSCLC
Metastatic carcinomas
0 (0%)
58 (72%)
23 (28%) 81
4 (3%)
78 (62%)
9 (7%)
35 (28%)
126 4
136 32 35
207
TC = tumor cells; IC = inflammatory (immune cells); TME = tumor microenvironment; NSCLC = non-small cell lung cancer.
Table 2. Significantly different TME categories* between NSCLC and metastatic carcinomas to the lung (p<0.001).
TML = tumor mutational load; SD = standard deviation
Table 3. Tumor mutational load differences* between the primary (NSCLC) and metastatic tumors to the lung (p<0.001); Metastatic melanomas** exhibited particularly high TML (mean: 32.70, SD: ).
Conclusions
Our study revealed significant differences in the presence of PD-L1 expressing cells in the microenvironments of primary NSCLC and metastatic to lungs carcinomas.
It also showed that the tumor mutational burdens differ between the primary and metastatic tumors to the lung.
These observations should be further explored for the refinement of the immune therapy treatment strategies, as the evidence emerges on the value of distinction between various cellular components in the tumor microenvironments for the purpose of selection of patients for the immune check point inhibition.
*Correspondence: