Age-related differences of immune infiltrates in pheochromocytomas and paragangliomas
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BRIEF REPORT
Age‑related differences of immune infiltrates in pheochromocytomas and paragangliomas S. Batchu1 Received: 4 August 2020 / Accepted: 30 September 2020 © Italian Society of Endocrinology (SIE) 2020
Keywords Tumor-infiltrating immune cells · Pheochromocytoma · Paraganglioma · RNA deconvolution
Introduction Pheochromocytomas and paragangliomas are rare catecholamine-secreting endocrine tumors deriving from chromaffin cells of the embryonic neural crest [1]. Although these tumors arise in different areas, with pheochromocytomas originating from the adrenal medulla and paragangliomas emerging from extra-adrenal areas most commonly from the abdomen and thorax, they are usually grouped together to underscore their indistinguishable morphology [2]. Pheochromocytomas and paragangliomas, hereafter referred as “PCPG,” have a reported annual incidence of 1 in 300,000 [3]. Due to their rarity, certain important clinical characteristics of these tumors have yet to be fully elucidated, namely immune infiltration. Tumor-infiltrating immune cells (TIICs) are found in numerous solid tumors and have been shown to correlate with clinical outcomes [4]. Mechanistic studies have examined the complex interactions between TIICs and malignant cancer cells in tumor stroma, further illuminating the clinical relevance since the immune system has dual roles in host defense and tumor progression [5]. Previous studies have placed PCPG into a class of tumors displaying increased macrophage infiltration [6, 7]. Specifically, these class of tumors were shown to have greater M2 macrophages along with lymphocytic depletion, consistent with a poorly cytotoxic phenotype [6].
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40618-020-01443-x) contains supplementary material, which is available to authorized users. * S. Batchu [email protected] 1
Cooper Medical School at Rowan University, 401 Broadway, Camden, NJ 08103, USA
Although these previous reports have suggested a general infiltrative signature, characterizing specific TIIC subpopulations exclusively in PCPG tumors has yet to be performed. To minimize this knowledge gap, the present study characterized 22 immune subpopulations from 179 primary PCPG tumors using an established machine-learning algorithm and revealed associations of certain TIICs with patient age.
Methods Data acquisition Level 3 RNA-sequencing RSEM non-normalized count data, somatic mutation data, and the corresponding clinical data matrix for 179 primary solid PCPG tumors were retrieved from Broad GDAC (https://gdac.broadinstitute.org/) originally developed by The Cancer Genome Atlas (TCGA) work group [8]. Of the 179 samples, 31 were paragangliomas and 148 were pheochromocytomas. Head and neck paragangliomas were not included in this cohort [8]. The RSEM counts were gene length normalized in TPM (transcripts per million) space prior to deconvolution.
Quantifying tumor‑infiltrating immune cells CIBERSORTx, an established machine-learning RNA deconvolutio
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