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Immunological signatures and predictive biomarkers for first-generation somatostatin receptor ligand resistance in Acromegaly

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Abstract

Purpose

Predicting resistance to first-generation Somatostatin Receptor Ligands (fg-SRL) in Acromegaly patients remains an ongong challenge. Tumor-associated immune components participate in various pathological processes, including drug-resistance. We aimed to identify the immune components involved in resistance of fg-SRL, and to investigate biomarkers that can be targeted to treat those drug-resistant Acromegaly.

Methods

We conducted a retrospective study involving 35 Acromegaly patients with somatotropinomas treated postoperatively with fg-SRL. Gathering clinicopathological data, SSTR2 expression, and immunological profiles, we utilized univariate, binary logistic regression, and ROC analyses to assess their predictive roles in fg-SRL resistance. Spearman correlation analysis further examined interactions among interested characteristics.

Results

19 patients (54.29%) exhibited resistance to postoperative fg-SRL. GH level at diagnosis, preoperative tumor volume, T2WI-MRI intensity, granularity, PD-L1, SSTR2, and CD8 + T cell infiltration showed association with clinical outcomes of fg-SRL. Notably, T2WI-MRI hyperintensity, PD-L1-IRS > 7, CD8 + T cell infiltration < 14.8/HPF, and SSTR2-IRS < 5.4 emerged as reliable predictors for fg-SRL resistance. Correlation analysis highlighted a negative relationship between PD-L1 expression and CD8 + T cell infiltration, while showcasing a positive correlation with preoperative tumor volume of somatotropinomas. Additionally, 5 patients with fg-SRL resistance underwent re-operation were involved. Following fg-SRL treatment, significant increases in PD-L1 and SSTR5 expression were observed, while SSTR2 expression decreased in somatotropinoma.

Conclusion

PD-L1 expression and CD8 + T cell infiltration, either independently or combined with SSTR2 expression and T2WI-MRI intensity, could form a predictive model guiding clinical decisions on fg-SRL employment. Furthermore, targeting PD-L1 through immunotherapy and embracing second-generations of SRL with higher affinity to SSTR5 represent promising strategies to tackle fg-SRL resistance in somatotropinomas.

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Data availability

No datasets were generated or analysed during the current study.

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Funding

This research was funded by the Hunan Provincial Natural Science Foundation of China (2021JJ40868), the National Natural Science Foundation of China (no.82001738), and the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University.

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China

    Mei Luo

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

    Mei Luo

  3. Department of Pediatric Dermatology, Dermatology Hospital of Southern Medical University, 510091, Guangzhou, China

    Jiangfan Yu

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

    Rui Tang

  5. Clinical Medical Research Center for Systemic Autoimmune Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Rui Tang

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Mei Luo, Jiangfan Yu, 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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Luo, M., Yu, J. & Tang, R. Immunological signatures and predictive biomarkers for first-generation somatostatin receptor ligand resistance in Acromegaly. J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04620-7

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