Comprehensive Analysis of Immunity to Pituitary Adenomas: Implications of Immunotherapeutic Approaches for Pituitary Adenomas

Background: Immunotherapy is a promising therapeutic approach for cancers. However, the immune background and the interactions between pituitary adenomas (PAs) and the host immune system remain unclear. Methods: Poly-A enriched RNA sequencing was performed on 115 snap frozen PA samples. Estimating the Proportion of Immune and Cancer cells (EPIC) was used to detect all the main cell types (B cells, CD8+ T cells, CD4+ T cells, macrophages and NK cells) in a tumor sample from the expression of genes. Immunohistochemical (IHC) staining was used to validate the main findings.   Findings: In RNA sequencing data, PA samples showed immune infiltration, including B cells, CD8+ T cells, CD4+ T cells, macrophages and NK cells. The results were further validated by IHC. Meanwhile, pathway analysis showed that TNFR superfamily (TNFRSF), IL-10 family and TGF beta (TGFβ) family were the potential mechanisms of immune infiltration in PAs. In order to search how tumor making progression with high infiltration of immune cells, gene-expression data revealed that tumor progression was related to increased expression of PD-1/PD-L1 and was associated with higher infiltration of CD8+ T cells. Besides, pathway enrichment analysis showed that regulation of death/apoptosis processes and the JAK-STAT pathway were found to be significantly enriched in samples with higher immune infiltration. At last, analysis of cancer-testis antigens (CTAs) expression in CD8+ T cells suggested that CTAG2 and TSPYL6 were potential immunotherapeutic targets in GH and non-functioning PAs, respectively. Interpretation: Our work provides new angles for understanding tumor-infiltrating immune cells. The results may inform effective checkpoint blockade and cancer vaccine therapies and make it possible to take immunotherapy into invasive functioning PAs. Funding Statement: This work was supported by the National Natural Science Foundation of China under Grant number 81471229; Capital Medical Development Research Foundation under Grant number 201811071. Declaration of Interests: No potential conflicts of interest are declared. Ethics Approval Statement: The PA tissue collection was approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University. All procedures involving human participants conformed to the ethical standards of the national research committee and the 2013 Helsinki Declaration, which were approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University. Informed consent was obtained from all patients prior to their enrollments in this study.