Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression

Yu, Mei; Bi, Wenya Linda; Agolia, James; Hu, Changchen; Larsen, Alexandra Giantini; Meredith, David M.; Abdulmohsen, Sally Al; Bale, Tejus; Dunn, Gavin P.; Abedalthagafi, Malak; Dunn, Ian F.

doi:10.1007/s11102-020-01114-3

Cited by 17 publications

(19 citation statements)

References 83 publications

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“…found that gonadotropin-secreting adenomas (n=12) had higher CD68 expression than other functional PAs (n=16) ( 33 ). Another specimen analysis including 44 NFPAs and 28 functional PAs revealed no significant difference in CD68+ cell infiltration between NFPAs and functional PAs, while among functional PAs, PRL-secreting adenomas had higher CD68+ cell infiltration than ACTH- and GH-secreting adenomas ( 32 ). Lu’s team, however, performed a more pathologically detailed analysis with 9 densely granulated GH-secreting adenomas, 9 sparsely granulated GH-secreting adenomas, 9 null cell adenomas and 8 ACTH-secreting adenomas.…”

Section: The Infiltration Of Macrophages In Human Pasmentioning

confidence: 91%

“…Meanwhile, they found that higher CD8+T and CD4+T infiltration corresponded to stronger tumor invasiveness and worse survival (58). Mei et al's results also suggested functional PAs had a higher CD4+T and CD8+T infiltration than NFPAs (32). From these results, functional PAs seem to attract more CD4+T and CD8+T cells than NFPAs.…”

Section: Exploration Of the Infiltration Patterns Of Macrophages In Different Subtypes Of Pamentioning

confidence: 96%

“…Recent studies have reported CD68+ macrophages in PAs at levels three times higher than those in the normal pituitary ( 32 , 33 ), and these cells are the most highly infiltrating immune cells in PAs ( 34 ). Detected mostly by immunohistochemistry, infiltrating macrophages vary greatly among different PA subtypes.…”

Section: The Infiltration Of Macrophages In Human Pasmentioning

confidence: 99%

“…A study of 72 PA specimens found that CD163 expression in tumors is related to inhibitory molecules, such as PD-L1, PD-L2, and LAG3 ( 32 ). Treatment with PA cell conditioned medium (CM) upregulated the expression of IL-10 and TGF-β in THP-1 cells, a monocytic cell line ( 35 ).…”

Section: Crosstalk Between Macrophages and Tumor Cells In The Pa-tmementioning

confidence: 99%

“…As mentioned above, the pattern of macrophage infiltration among different subtypes of PAs has not been established. The infiltration of CD68+ cells and CD163+ cells in NFPAs and functional PAs varies among different studies ( 32 , 33 , 35 ). NFPAs include tumors with a variety of pathological classifications.…”

Section: Future Prospectsmentioning

confidence: 99%

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Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches

Han

Lin

et al. 2021

Front. Endocrinol.

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Macrophages are one of the most common infiltrating immune cells and an essential component of tumor microenvironment. Macrophages and the soluble cytokines and chemokines produced play an important role in tumorigenesis, progression, invasion and metastasis in solid tumors. Despite the multiple studies in other solid tumors, there is little known about macrophages in pituitary adenomas. Recently, studies about pituitary adenoma-infiltrated macrophages have been emerging, including the immunohistochemical and immunophenotypic analysis of the pituitary adenomas and further studies into the mechanism of the crosstalk between macrophages and tumor cells in vivo and in vitro. These studies have offered us new insights into the polarization of macrophages and its role in tumorigenesis, progression and invasion of pituitary adenomas. This review describes the advances in the field of pituitary adenoma-infiltrated macrophages and the prospect of targeting macrophages as cancer therapy in pituitary adenoma.

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Section: The Infiltration Of Macrophages In Human Pasmentioning

confidence: 91%

Section: Exploration Of the Infiltration Patterns Of Macrophages In Different Subtypes Of Pamentioning

confidence: 96%

Section: The Infiltration Of Macrophages In Human Pasmentioning

confidence: 99%

Section: Crosstalk Between Macrophages and Tumor Cells In The Pa-tmementioning

confidence: 99%

Section: Future Prospectsmentioning

confidence: 99%

See 3 more Smart Citations

Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches

Han

Lin

et al. 2021

Front. Endocrinol.

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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

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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.

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