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Comprehensive analysis of the immunological landscape of pituitary adenomas: implications of immunotherapy for pituitary adenomas

  • Clinical Study
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Abstract

Purposes

Immunotherapies for solid tumor are gaining traction in the clinic, however, the immunological landscape of pituitary adenomas (PAs) is not well defined. In the present study, we used the RNA-seq data of PAs to investigate the impact of immunological landscape on clinical features of pituitary adenomas and aim to evaluate the potential immunotherapy for PAs.

Methods

We analyzed tumor-infiltrating immune cells in 115 PA samples using RNA-seq. Main immune cell types (B cells, CD8+ T cells, CD4+ T cells, macrophages and NK cells) were detected from the expression of genes. The association between immune cells abundance and immune checkpoint, as well as inflammatory factors were analyzed. 10 additional patients were enrolled for validation.

Results

In RNA sequencing data, landscape of PAs were identified. Our computationally inferred immune infiltrates significantly associate with patient clinical features. Growth hormone-secreting adenomas (GHomas) were found with higher B cells and CD8+ T cells infiltration. Moreover, GHomas showed relative different genetic background, significant invasive behavior and independently correlated with reduced progress-free time. Tumor progression was related to increased expression of PD-1/PD-L1 and was associated with higher immune infiltration. Analysis of cancer-testis antigen expression and CD8+ T-cell abundance suggested CTAG2 and TSPYL6 were potential immunotherapeutic targets in GHomas and non-functioning adenomas, respectively.

Conclusions

Tumor-infiltrating immune cells confer important clinical and biological implications. Our results of immune-infiltrate levels in PAs may inform effective cancer vaccine and checkpoint blockade therapies and make it possible to take immunotherapy into invasive PAs.

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Data availability

Data available on request from the authors.

Code availability

Not applicable.

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Funding

This work was financially supported by the Beijing Municipal Health Commission of China (Grant No. PXM2019_026280_000002, Recipient: Wang Jia).

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Wenjianlong Zhou, Chuanbao Zhang, Dainan Zhang, Jiayi Peng, Xi Wang, Xiudong Guan, Deling Li, Guijun Jia & Wang Jia

  2. Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Wenjianlong Zhou

  3. China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China

    Shunchang Ma & Wang Jia

  4. Beijing Neurosurgical Institute, 199 West Road, South Fourth Ring Road, Beijing, China

    Shunchang Ma & Wang Jia

  5. Beijing Ditan Hospital, Beijing, China

    Peiliang Li

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Contributions

WZ—Conception and design, Acquisition of data, Development of methodology, Analysis and interpretation of data, Writing, review and/or revision of the manuscript, Administrative, technical, or material support. CZ—Conception and design, Acquisition of data, Development of methodology, Analysis and interpretation of data, Writing, review and/or revision of the manuscript, Administrative, technical, or material support. WJ—Conception and design, Writing, review and/or revision of the manuscript, Administrative, technical, or material support, Study supervision. ZD—Development of methodology. JP—Development of methodology. SM—Acquisition of data. XW—Acquisition of data. XG—Acquisition of data. JD—Analysis and interpretation of data. JN—Analysis and interpretation of data. GJ—Writing, review and/or revision of the manuscript, Administrative, technical, or material support. DL—Administrative, technical, or material support. All authors read and approved the final manuscript.

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Correspondence to Wang Jia.

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Zhou, W., Zhang, C., Zhang, D. et al. Comprehensive analysis of the immunological landscape of pituitary adenomas: implications of immunotherapy for pituitary adenomas. J Neurooncol 149, 473–487 (2020). https://doi.org/10.1007/s11060-020-03636-z

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