Adrenal (Excluding Mineralocorticoids)

SAT-485 - Characterisation of Tumor-Associated Macrophages (TAM) Polarisation in Adrenocortical Tumors

Saturday, June 13, 2026

9:30 AM - 4:30 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

Rosa Catalano, PhD (she/her/hers)

University of Milan
Milan, ITALY

Co-Author(s)

CM

Cynthia Mendoza Pimentel, Student

University Hospital, University of Würzburg
Würzburg, Germany
MD

Mario Detomas, MD (he/him/his)

Dept. of Medicine, University Hospital, University of Würzburg, Division of Endocrinology and Diabetes, Würzburg, Germany
Wrzburg, Germany
Otilia Kimpel, MD

Clinician scientist
Department of Endocrinology, University Hospital Wrzburg
Wrzburg, Germany
MS

Marc P. Schauer, Student

University Hospital, University of Würzburg
Würzburg, Germany
GC

Giacomo Cristofolini, MD

University Hospital, University of Würzburg
Würzburg, Germany
AS

Ali Kerim Secener, Doctoral candidate

Max Delbrück Center for Molecular Medicine
Berlin, Germany
SK

Sarah Küppers, MD

University Hospital, University of Würzburg
Würzburg, Germany
SS

Sonja Steinhauer, NA

laboratory technician
University Hospital, University of Würzburg
Würzburg, Germany
SH

Sabine Herterich, NA

laboratory technician
Central Laboratory University Hospital Würzburg
Würzburg, Germany
SK

Stefan Kircher, MD

Institute of Pathology, University of Würzburg
Würzburg, Germany
CR

Cristina L Ronchi, MD, PhD

Professor
University of Birmingham
Birmingham, United Kingdom
SS

Silviu Sbiera, PhD

Dept. of Medicine, University Hospital, University of Würzburg, Division of Endocrinology and Diabetes, Würzburg, Germany
Würzburg, Germany
Erika Peverelli, PhD (she/her/hers)

University of Milan
Cislago, ITALY
Giovanna Mantovani, MD, PhD (she/her/hers)

Full Professor of Endocrinology
University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, ITALY
MF

Martin Fassnacht, MD

University of Wuerzburg
Würzburg, Germany

Senior Author/Primary Investigator(s)

BA

Barbara Altieri, MD (she/her/hers)

Dept. of Medicine, University Hospital, University of Würzburg, Division of Endocrinology and Diabetes, Würzburg, Germany
Wrzburg, Germany

Co-Author(s)

BA

Barbara Altieri, MD (she/her/hers)

Dept. of Medicine, University Hospital, University of Würzburg, Division of Endocrinology and Diabetes, Würzburg, Germany
Wrzburg, Germany

Disclosure(s):

Rosa Catalano, PhD: No financial relationships to disclose

Otilia Kimpel, MD: No financial relationships to disclose

Erika Peverelli, PhD: No financial relationships to disclose

Background:
Macrophages infiltration is gaining increasing attention in adrenocortical tumors. However, a comprehensive overview on tumor-associated macrophages (TAM) and macrophages polarization across adrenocortical tissues is still lacking.

Aim:
To characterize macrophages infiltration in normal adrenal glands (NAG) and TAM in adrenocortical adenomas (ACA) and carcinomas (ACC) and investigate association with clinicopathological features.

Methods:
We performed immunohistochemistry (IHC) for CD68 (M1-M2 marker), CD16 (immune-infiltration marker), CD163 and CD206 (M2-specific markers), and CD204 (TAM-marker) in 102 ACA, 153 ACC and 16 ACA-adjacent NAG. Immunostaining was quantified using QuPath-0.5.1 pixel classification and reported as percentage of positive pixels. In all ACA, oncogenic variants in CTNNB1, PRKACA, and GNAS were assessed by Sanger sequencing. Differences in macrophages infiltration were investigated among all tissues. TAM associations with clinicopathological parameters and circulating white blood cell count were analyzed in ACA; analyses in ACC are ongoing. Myeloid profile was further explored in single-nucleus RNA sequencing (snRNA-Seq, DOI:10.1002/ctm2.1798) using Seurat.

Results:
In NAG, median CD68 expression (2.4%) was lower than all other markers (CD16=10.3%, CD163=5.8%, CD206=7.4%, and CD204=8.2%; p< 0.001). ACA showed higher CD16 (6.2%), CD163 (6.6%), and CD204 (7.9%) than CD206 and CD68 (both 1.6%, p< 0.001). Matched ACA-NAG comparison revealed in ACA reduced CD206 expression at both IHC and snRNA-Seq (p < 0.001). Consistently, CD163/CD206 ratio was elevated in ACA (3.11 vs 0.84, p< 0.001) indicating a shift toward CD163 polarization. In ACC, CD68 (1.7%) and CD163 (2.7%) were lower than CD204 (5.2%) and CD16 (5.3%); analysis on CD206 is ongoing. Compared to ACA, ACC had lower CD204 and CD163 (p < 0.001), but similar CD68 and CD16.
In endocrine inactive but not in cortisol-secreting ACA (CPA), CD68, CD16 and CD204 expression was inversely correlated with circulating lymphocyte to monocytes ratio (all p< 0.05). Cortisol excess was associated with CD68 and CD16, and in CPA only, drove a CD163+/CD206- polarisation shift (all p< 0.05). In women, CD163/CD206 moderately correlated with cortisol after 1 mg-DST (ρ=0.27, p=0.04), and CD206/CD16 was lower in CPA (p=0.01), suggesting sex-specific immune modulation.
ACA with PRKACA oncogenic variant showed lower CD206 and CD16 (p < 0.01) compared to those without. These associations remained significant within CPA and were confirmed by multivariate logistic regression, supporting a PRKACA-driven effect.

Conclusion: TAM showed distinct polarization patterns with a decreasing trend in the investigated markers from NAG to ACA and ACC. In ACA, this immunophenotype could be modulated by cortisol, sex, and PRKACA, highlighting the intricate heterogeneity of TAM in adrenocortical tumors.

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