Targeting the tumor immune microenvironment could become a potential therapeutic modality for aggressive pituitary adenoma

Abstract Purpose This study aimed to explore the relationship between the aggressiveness and immune cell infiltration in pituitary adenoma (PA) and provide the basis for immuno-targeting therapies. Methods One hundred three patients with PA who underwent surgery at a single institution were retrospectively identified. The infiltration of macrophages and T-lymphocytes was quantitatively assessed. Results The number of CD68 + macrophages was positively correlated with Knosp (P = 0.003) and MMP-9 expression grades (P = 0.00). The infiltration of CD163 + macrophages differed among Knosp (P = 0.022) and MMP-9 grades (P = 0.04). CD8 + tumor-infiltrating lymphocytes (TILs) were also positively associated with Knosp (P = 0.002) and MMP-9 grades (P = 0.01). Interestingly, MGMT expression was positively correlated with MMP-9 staining extent (P = 0.000). The quantities of CD8 + TILs (P = 0.016), CD68 + macrophages (P = 0.000), and CD163 + macrophages (P = 0.043) were negatively associated with MGMT expression levels. The number of CD68 + macrophages in the PD-L1 negative group was significantly more than that in the PD-L1 positive group (P = 0.01). The rate of PD-L1 positivity was positively correlated with the Ki-67 index (P = 0.046) and p53 expression (P = 0.029). Conclusion Targeted therapy for macrophages and CD8 + TILs could be a helpful treatment in the future for aggressive PA. Temozolomide (TMZ) may have better effects on the treatment of PAs with greater immune cell infiltration. Anti-PD-L1 therapy may better respond to PAs with higher Ki-67 and p53 expression and more infiltrating CD68 + macrophages. Multiple treatment modalities, especially combined immunotherapy, or combination immunotherapy with TMZ, could become a novel therapeutic strategy for aggressive PA.