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

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Abstract

Purpose

Tumor immune microenvironment in pituitary neuroendocrine tumors (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 tumor immune microenvironment (TIME), thus promoting the application of current immunotherapy for aggressive and metastatic PitNETs.

Methods

Immunocyte infiltration 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.

Results

Transcriptome profiles from 210 PitNETs/ 8 normal pituitaries (NPs) and immunohistochemical validations of 77 PitNETs/6 NPs revealed a significant increase in M2-macrophage infiltration in PIT1-lineage 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 infiltration 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 CTLA-4) 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.

Conclusion

PIT1-lineage PitNETs exhibit a distinct immune profile with enrichment of M2 macrophage infiltration and PD-L1 expression, which may contribute to its clinical aggressiveness. Application of current immune checkpoint inhibitors and M2-targeted immunotherapy might be more beneficial to treat aggressive and metastatic PIT-lineage PitNETs.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was funded by the Human Provincial Natural Science Foundation of China (2021JJ40868) and the National Natural Science Foundation of China (no.82001738).

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Authors and Affiliations

  1. Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Mei Luo & Haijun Wang

  2. Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Rui Tang

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Mei Luo and Rui Tang. The first draft of the manuscript was written by Mei Luo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rui Tang or Haijun Wang.

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Research involving human participants, their data or biological materials were reviewed and approved by Medical Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University (protocol number [2022] 229-1).

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Luo, M., Tang, R. & Wang, H. Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs): increased M2 macrophage infiltration and PD-L1 expression in PIT1-lineage subset. J Neurooncol 163, 663–674 (2023). https://doi.org/10.1007/s11060-023-04382-8

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