Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer : Implications for immunotherapy
Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray. Immunostaining for PD-L1 and 2 was evaluated in paired primary and metastatic lesions and correlated with clinicopathologic features. Results: We included 98 patients with non-small cell (NSCLC, n = 65, 66%), small cell histology (SCLC, n = 29, 30%) and four (4%) atypical carcinoids (AC). In total 8/65 (12%) primary PD-L1 positive NSCLC, had discordant matched metastases (14/17, 82%). PD-L1 negative primaries had universally concordant distant metastases. SCLCs were universally PD-L1 negative across primary and metastatic disease. PD-L2 positive NSCLC (n = 11/65, 17%) had high rate of discordant metastases (n = 24/27, 88%) and four cases (6%) had PD-L2 positive metastases with negative primaries. 2/29 SCLC (7%) and 1/4 AC (25%) were PD-L2 positive with discordance in all the sampled metastatic sites (n = 5). We found no correlation between the expression of PD ligands and clinicopathologic features of LC. Conclusions: Intra-tumoral heterogeneity in the expression of PD ligands is common in NSCLC, while PD-L1 is homogeneously undetectable in primary and metastatic SCLC. This holds implications in the clinical development of immune response biomarkers in LC.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Oncoimmunology - 5(2016), 9 vom: 28., Seite e1213934 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pinato, David J [VerfasserIn] |
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| Themen: |
Heterogeneity |
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| Anmerkungen: |
Date Revised 10.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM265449707 |
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| 100 | 1 | |a Pinato, David J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer |b Implications for immunotherapy |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Revised 10.03.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray. Immunostaining for PD-L1 and 2 was evaluated in paired primary and metastatic lesions and correlated with clinicopathologic features. Results: We included 98 patients with non-small cell (NSCLC, n = 65, 66%), small cell histology (SCLC, n = 29, 30%) and four (4%) atypical carcinoids (AC). In total 8/65 (12%) primary PD-L1 positive NSCLC, had discordant matched metastases (14/17, 82%). PD-L1 negative primaries had universally concordant distant metastases. SCLCs were universally PD-L1 negative across primary and metastatic disease. PD-L2 positive NSCLC (n = 11/65, 17%) had high rate of discordant metastases (n = 24/27, 88%) and four cases (6%) had PD-L2 positive metastases with negative primaries. 2/29 SCLC (7%) and 1/4 AC (25%) were PD-L2 positive with discordance in all the sampled metastatic sites (n = 5). We found no correlation between the expression of PD ligands and clinicopathologic features of LC. Conclusions: Intra-tumoral heterogeneity in the expression of PD ligands is common in NSCLC, while PD-L1 is homogeneously undetectable in primary and metastatic SCLC. This holds implications in the clinical development of immune response biomarkers in LC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Heterogeneity | |
| 650 | 4 | |a PD-1 | |
| 650 | 4 | |a PD-L1 | |
| 650 | 4 | |a PD-L2 | |
| 650 | 4 | |a lung cancer | |
| 700 | 1 | |a Shiner, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a White, Solomon D T |e verfasserin |4 aut | |
| 700 | 1 | |a Black, James R M |e verfasserin |4 aut | |
| 700 | 1 | |a Trivedi, Pritesh |e verfasserin |4 aut | |
| 700 | 1 | |a Stebbing, Justin |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Rohini |e verfasserin |4 aut | |
| 700 | 1 | |a Mauri, Francesco A |e verfasserin |4 aut | |
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