Abstract
BACKGROUND: The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases.
EXPERIMENTAL DESIGN: Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ(2) or Fisher's exact test were used for analysis.
RESULTS: We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009).
CONCLUSIONS: We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1953-1958 |
| Number of pages | 6 |
| Journal | Annals of oncology : official journal of the European Society for Medical Oncology |
| Volume | 27 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2016 |
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Keywords
- heterogeneity
- lung cancer
- metastasis
- PD-L1
- tumor immunology
ASJC Scopus subject areas
- Hematology
- Oncology
Cite this
Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. / Mansfield, Aaron; Aubry, M. C.; Moser, J. C.; Harrington, S. M.; Dronca, Roxana S; Park, Sean S; Dong, Haidong M.
In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 27, No. 10, 01.10.2016, p. 1953-1958.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer
AU - Mansfield, Aaron
AU - Aubry, M. C.
AU - Moser, J. C.
AU - Harrington, S. M.
AU - Dronca, Roxana S
AU - Park, Sean S
AU - Dong, Haidong M
PY - 2016/10/1
Y1 - 2016/10/1
N2 - BACKGROUND: The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases.EXPERIMENTAL DESIGN: Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ(2) or Fisher's exact test were used for analysis.RESULTS: We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009).CONCLUSIONS: We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.
AB - BACKGROUND: The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases.EXPERIMENTAL DESIGN: Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ(2) or Fisher's exact test were used for analysis.RESULTS: We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009).CONCLUSIONS: We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.
KW - heterogeneity
KW - lung cancer
KW - metastasis
KW - PD-L1
KW - tumor immunology
UR - http://www.scopus.com/inward/record.url?scp=85014431333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014431333&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdw289
DO - 10.1093/annonc/mdw289
M3 - Article
VL - 27
SP - 1953
EP - 1958
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 10
ER -