Single-cell transcriptomics link gene expression signatures to clinicopathological features of gonadotroph and lactotroph PitNET

T Elise Potthoff ¹, Carolin Walter ², Daniela Jeising ¹

¹Department of Paediatric Haematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
²Institute of Medical Informatics, University of Münster, 48149, Münster, Germany.
³Department of Neurosurgery, University Hospital of Münster, 48149, Münster, Germany.
⁴Institute of Medical Informatics, Heidelberg University Hospital, Heidelberg, Germany.
⁵Division of Translational Pathology, Gerhard Domagk Institute of Pathology, University Hospital Münster, 48149, Münster, Germany.
⁶Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
⁷Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
⁸Research Institute Children's Cancer Center, 20251, Hamburg, Germany.
⁹DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (iFIT), University of Tübingen, 72076, Tübingen, Germany.
¹⁰Department of Pediatric Hematology and Oncology, University Hospital Tübingen, 72076, Tübingen, Germany.
¹¹German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site, Tuebingen, Germany.
¹²Department of Paediatric Haematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany. Kornelius.Kerl@ukmuenster.de.

⁰Department of Paediatric Haematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Journal of Translational Medicine +

|

November 16, 2024

View abstract on PubMed

Summary

Aggressive pituitary tumors (PitNET) show distinct immune cell profiles. Proliferative lymphocytes correlate with aggression, while CD8+ T and NK cells may offer anti-tumor effects and immunotherapy targets.

Area Of Science

Endocrinology
Oncology
Immunology

Background

Pituitary neuroendocrine tumors (PitNET) are common intracranial tumors with variable behavior.
Tumor microenvironment (TME) influences PitNET aggressiveness, but its cellular components are not fully understood.
Understanding TME in PitNET is crucial for predicting and managing aggressive tumor behavior.

Purpose Of The Study

To comparatively characterize the transcriptome and TME of gonadotroph PitNET (GoPN) and lactotroph PitNET (LaPN).
To correlate cellular composition with clinical features and aggressive tumor behavior.
To identify potential therapeutic targets for aggressive PitNET.

Main Methods

Single-cell RNA sequencing for transcriptome analysis of PitNET subtypes.
Differential gene expression analysis and gene expression program identification.
Bulk RNA-seq and immunostaining for TME composition and immune cell infiltration quantification.

Main Results

Lactotroph PitNET exhibit a proliferative gene profile associated with aggressive growth.
Distinct TME compositions were observed: GoPN enriched with SPP1+ macrophages and CD4+ T cells; LaPN with CD4/CD8 double-negative T cells and NK cells.
Proliferative lymphocytes correlated with increased aggressiveness, while CD8+ T and NK cells showed potential anti-tumoral effects.

Conclusions

Significant differences in cellular composition exist between GoPN and LaPN subtypes.
Lymphoid cells play a role in the variable aggressive behavior of PitNET.
Proliferative lymphocytes, CD8+ T cells, and NK cells are potential targets for novel PitNET immunotherapies.

Keywords:

Gonadotroph Intratumoral heterogeneity Lactotroph Pituitary neuroendocrine tumor (PitNET) Single-cell RNA sequencing Tumor microenvironment

Related Concept Videos

Cell Specific Gene Expression