Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches

Han, Changxi; Lin, Sheng; Lu, Xingyu; Xue, Li; Wu, Zhe

doi:10.3389/fendo.2021.785050

Cited by 12 publications

(2 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growing evidence has suggested that immune cells, particularly macrophages, play an essential role in the development and progression of pituitary adenomas [ 21 , 22 ]. Macrophages are present in both normal pituitary and PitNETs, and their types and populations vary depending on the subtype of PitNETs [ 23 – 25 ]. M2 macrophages are prevalent in the pituitary gland and may play a role in tumorigenesis [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Lin,

Dai,

Han

et al. 2024

Genome Med

Self Cite

View full text Add to dashboard Cite

Background Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. Methods The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. Results The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. Conclusions In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.

show abstract

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Lin,

Dai,

Han

et al. 2024

Genome Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pituitary adenoma is the second most common intracranial tumor, with an incidence of 15% ( 1 ). Although they are benign, nearly 35–40% of pituitary adenomas are invasive ( 2 , 3 ). These adenomas are large; invade the cavernous sinus, sphenoid sinus, and clivus; are prone to recurrence after surgery; and are resistant to conventional treatments, resulting in a more difficult treatment regimen ( 2 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Characteristics and M2 Macrophage Infiltrates in Invasive Nonfunctioning Pituitary Adenomas

et al. 2022

View full text Add to dashboard Cite

ObjectiveThe aim of this study was to investigate the metabolic differences between invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs), determine the expression of an M2 macrophage marker in NFPAs, and analyze the effects of metabolic changes in invasive NFPAs on M2 macrophage infiltrates.MethodsTissue samples of NFPAs from patients who underwent transsphenoidal or craniotomy surgery from January 2021 to August 2021 were collected. NFPA tissues were analyzed based on a gas chromatography-mass spectrometry non-targeted metabolomics platform, and immunohistochemical staining for M2 macrophage marker CD206 was performed.ResultsWe evaluated 15 invasive and 21 non-invasive NFPAs. A total of 22 metabolites were identified through non-targeted metabolomics analysis. Among them, the expression of 1-octadecanol, inosine 5’-monophosphate, adenosine 5’-monophosphate, guanosine 5’-monophosphate, creatinine, desmosterol, taurine, hypotaurine, lactic acid, and succinic acid was upregulated in invasive NFPAs, while that of 1-oleoylglycerol, arachidonic acid, cis-11-eicosenoic acid, docosahexaenoic acid, glyceric acid, hypoxanthine, linoleic acid, lysine, oleic acid, uracil, valine, and xanthine was downregulated. Immunohistochemical analysis suggested that the number of CD206-positive cells was higher in invasive NFPAs than in non-invasive NFPAs.ConclusionInvasive and non-invasive NFPAs showed distinct metabolite profiles. The levels of succinic acid and lactic acid were higher in invasive NFPAs, and the high expression of the M2 macrophage marker was verified in invasive NFPAs.

show abstract

Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs): increased M2 macrophage infiltration and PD-L1 expression in PIT1-lineage subset

Luo¹,

Tang

Wang³

2023

J Neurooncol

View full text Add to dashboard Cite

Tumor immune microenvironment in PitNETs and application of current immunotherapy for refractory PitNETs remains debated. We aim to evaluate the immune landscape in different lineages of PitNETs and determine the potential role of pituitary transcription factors in reshaping the TIME, thus promoting the application of current immunotherapy for aggressive and metastatic PitNETs. MethodsImmunocyte in ltration and expression patterns of immune checkpoint molecules in different lineages of PitNETs were estimated via in silico analysis and validated using an IHC validation cohort. The correlation between varying immune components with clinicopathological features was assessed in PIT1-lineage PitNETs. ResultsTranscriptome pro les from 210 PitNETs/ 8 normal pituitaries (NPs) and immunohistochemical validations of 77 PitNETs/ 6 NPs revealed a signi cant increase in M2-macrophage in ltration in PIT1lineage PitNETs, compared with the TPIT-lineage, SF1-lineage subsets and NPs. While CD68 + macrophage, CD4 + T cells, and CD8 + T cells were not different among them. Increased M2-macrophage in ltration was associated with tumor volume (p < 0.0001, r = 0.57) in PIT1-lineage PitNETs. Meanwhile, differentially expressed immune checkpoint molecules (PD-L1, PD1, and CTLA4) were screened and validated in IHC cohorts. The results showed that PD-L1 was highly expressed in PIT1-lineage subsets, and PD-L1 overexpression showed a positive correlation with tumor volume (p = 0.04, r = 0.29) and cavernous sinus invasion (p < 0.0001) in PIT1-lineage PitNETs. ConclusionPIT1-lineage PitNETs exhibit a distinct immune pro le with enrichment of M2 macrophage in ltration and PD-L1 expression, which contribute to its clinical aggressiveness. Application of current immune checkpoint inhibitors and M2-targeted immunotherapy might be more bene cial to treat aggressive and metastatic PIT-lineage PitNETs.

show abstract

Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches

Cited by 12 publications

References 84 publications

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors

Metabolic Characteristics and M2 Macrophage Infiltrates in Invasive Nonfunctioning Pituitary Adenomas

Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs): increased M2 macrophage infiltration and PD-L1 expression in PIT1-lineage subset

Contact Info

Product

Resources

About