PD-L1 expression and association with genetic background in pheochromocytoma and paraganglioma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F22%3A00565106" target="_blank" >RIV/86652036:_____/22:00565106 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10451157 RIV/00216208:11310/22:10451157

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fonc.2022.1045517/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fonc.2022.1045517/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2022.1045517" target="_blank" >10.3389/fonc.2022.1045517</a>

Jazyk výsledku

angličtina

Název v původním jazyce

PD-L1 expression and association with genetic background in pheochromocytoma and paraganglioma

Popis výsledku v původním jazyce

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors associated with poor prognosis and limited therapeutic options. Recent advances in oncology-related immunotherapy, specifically in targeting of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathways, have identified a new treatment potential in a variety of tumors, including advanced and rare tumors. Only a fraction of patients being treated by immune checkpoint inhibitors have shown to benefit from it, displaying a need for strategies which identify patients who may most likely show a favorable response. Building on recent, promising outcomes in a clinical study of metastatic PPGL using pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting the PD-1/PD-L1 pathway, we examined PD-L1 and PD-L2 expression in relation to oncogenic drivers in our PPGL patient cohort to explore whether expression can predict metastatic potential and/or be considered a predictive marker for targeted therapy. We evaluated RNA expression in the NIH cohort of 48 patients with known genetic predisposition (sporadic, pseudohypoxia: SDHB, VHL, EPAS1, EGLN1, kinase signaling: RET, NF1) and 6 normal medulla samples (NAM). For comparison, 72 PPGL samples from The Cancer Genome Atlas (TCGA) were used for analysis of gene expression based on the variant status (pseudohypoxia: SDHB, VHL, EPAS1, EGLN1, kinase signaling: NF1, RET). Expression of PD-L1 was elevated in the PPGL cohort compared to normal adrenal medulla, aligning with the TCGA analysis, whereas PD-L2 was not elevated. However, expression of PD-L1 was lower in the pseudohypoxia cluster compared to the sporadic and the kinase signaling subtype cluster, suggesting that sporadic and kinase signaling cluster PPGLs could benefit from PD-1/PD-L1 therapy more than the pseudohypoxia cluster. Within the pseudohypoxia cluster, expression of PD-L1 was significantly lower in both SDHB- and non-SDHB-mutated tumors compared to sporadic tumors. PD-L1 and PD-L2 expression was not affected by the metastatic status. We conclude that PD-L1 and PD-L2 expression in our cohort of PPGL tumors was not linked to metastatic behavior, however, the presence of PPGL driver mutation could be a predictive marker for PD-L1-targeted therapy and an important feature for further clinical studies in patients with PPGL.

Název v anglickém jazyce

PD-L1 expression and association with genetic background in pheochromocytoma and paraganglioma

Popis výsledku anglicky

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors associated with poor prognosis and limited therapeutic options. Recent advances in oncology-related immunotherapy, specifically in targeting of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathways, have identified a new treatment potential in a variety of tumors, including advanced and rare tumors. Only a fraction of patients being treated by immune checkpoint inhibitors have shown to benefit from it, displaying a need for strategies which identify patients who may most likely show a favorable response. Building on recent, promising outcomes in a clinical study of metastatic PPGL using pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting the PD-1/PD-L1 pathway, we examined PD-L1 and PD-L2 expression in relation to oncogenic drivers in our PPGL patient cohort to explore whether expression can predict metastatic potential and/or be considered a predictive marker for targeted therapy. We evaluated RNA expression in the NIH cohort of 48 patients with known genetic predisposition (sporadic, pseudohypoxia: SDHB, VHL, EPAS1, EGLN1, kinase signaling: RET, NF1) and 6 normal medulla samples (NAM). For comparison, 72 PPGL samples from The Cancer Genome Atlas (TCGA) were used for analysis of gene expression based on the variant status (pseudohypoxia: SDHB, VHL, EPAS1, EGLN1, kinase signaling: NF1, RET). Expression of PD-L1 was elevated in the PPGL cohort compared to normal adrenal medulla, aligning with the TCGA analysis, whereas PD-L2 was not elevated. However, expression of PD-L1 was lower in the pseudohypoxia cluster compared to the sporadic and the kinase signaling subtype cluster, suggesting that sporadic and kinase signaling cluster PPGLs could benefit from PD-1/PD-L1 therapy more than the pseudohypoxia cluster. Within the pseudohypoxia cluster, expression of PD-L1 was significantly lower in both SDHB- and non-SDHB-mutated tumors compared to sporadic tumors. PD-L1 and PD-L2 expression was not affected by the metastatic status. We conclude that PD-L1 and PD-L2 expression in our cohort of PPGL tumors was not linked to metastatic behavior, however, the presence of PPGL driver mutation could be a predictive marker for PD-L1-targeted therapy and an important feature for further clinical studies in patients with PPGL.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Oncology

ISSN

2234-943X

e-ISSN

2234-943X

Svazek periodika

12

Číslo periodika v rámci svazku

NOV 11 2022

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

7

Strana od-do

1045517

Kód UT WoS článku

000889663700001

EID výsledku v databázi Scopus

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