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12.11.2022 | Original Article

Immune signature of pheochromocytoma and paraganglioma in context of neuroendocrine neoplasms associated with prognosis

verfasst von: Suman Ghosal, Katerina Hadrava Vanova, Ondrej Uher, Shaoli Das, Mayank Patel, Leah Meuter, Thanh-Truc Huynh, Abhishek Jha, Sara Talvacchio, Marianne Knue, Tamara Prodanov, Martha A. Zeiger, Naris Nilubol, David Taieb, Joakim Crona, Uma T. Shankavaram, Karel Pacak

Erschienen in: Endocrine | Ausgabe 1/2023

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Abstract

Purpose

To understand prognostic immune cell infiltration signatures in neuroendocrine neoplasms (NENs), particularly pheochromocytoma and paraganglioma (PCPG), we analyzed tumor transcriptomic data from The Cancer Genome Atlas (TCGA) and other published tumor transcriptomic data of NENs.

Methods

We used CIBERSORT to infer immune cell infiltrations from bulk tumor transcriptomic data from PCPGs, in comparison to gastroenteropancreatic neuroendocrine tumors (GEPNETs) and small cell lung carcinomas (SCLCs). PCPG immune signature was validated with NanoString immune panel in an independent cohort. Unsupervised clustering of the immune infiltration scores from CIBERSORT was used to find immune clusters. A prognostic immune score model for PCPGs and the other NENs were calculated as a linear combination of the estimated infiltration of activated CD8⁺/CD4⁺ T cells, activated NK cells, and M0 and M2 macrophages.

Results

In PCPGs, we found five dominant immune clusters, associated with M2 macrophages, monocytes, activated NK cells, M0 macrophages and regulatory T cells, and CD8⁺/CD4⁺ T cells respectively. Non-metastatic tumors were associated with activated NK cells and metastatic tumors were associated with M0 macrophages and regulatory T cells. In GEPNETs and SCLCs, M0 macrophages and regulatory T cells were associated with unfavorable outcomes and features, such as metastasis and high-grade tumors. The prognostic immune score model for PCPGs and the NENs could predict non-aggressive and non-metastatic diseases. In PCPGs, the immune score was also an independent predictor of metastasis-free survival in a multivariate Cox regression analysis.

Conclusion

The transcriptomic immune signature in PCPG correlates with clinical features like metastasis and prognosis.

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Titel: Immune signature of pheochromocytoma and paraganglioma in context of neuroendocrine neoplasms associated with prognosis
verfasst von: Suman Ghosal
Katerina Hadrava Vanova
Ondrej Uher
Shaoli Das
Mayank Patel
Leah Meuter
Thanh-Truc Huynh
Abhishek Jha
Sara Talvacchio
Marianne Knue
Tamara Prodanov
Martha A. Zeiger
Naris Nilubol
David Taieb
Joakim Crona
Uma T. Shankavaram
Karel Pacak
Publikationsdatum: 12.11.2022
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 1/2023
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-022-03218-1

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