Table 1.
Immune studies of PAs
| Cell type and marker | Conclusion/distribution | Ref. | Population | Methods | Year |
|---|---|---|---|---|---|
| CD3 (T cells) | FPAs > NFPAs; GH adenomas > ACTH adenomas > PRL adenomas. | [5, 49] | 67; 48 | Immunohistochemistry | 2020; 2016 |
| CD4 (T cells) | FPAs > NFPAs; GH adenomas > non-GH adenomas. T cell phenotype was the CD4+ memory resting phenotype. May have angiogenic effects. | [32, 41, 48, 49] | 24; 134; 35; 48 | Immunohistochemistry | 2020 ;2020; 2015; 2016 |
| CD8 (T cells) | GH adenomas > non-GH adenomas. Positively correlated with serum PRL and intratumoral immunostaining of PRL and GH. Cavernous sinus invasion > non-invasive tumors. The number of CD8+ lymphocytes was positively correlated with the number of CD68+ macrophages. FPAs > NFPAs (especially GHomas). Cushing pituitary tumors had higher CD8+ T cells. | [41, 42, 48, 50–52] | 134; 191; 35; 27; 64; 115 |
Immunohistochemistry; Computational approach; RNA-seq.; |
2020; 2018; 2015; 2019; 2020; 2020 |
| FOXP3 (regulatory T cells) | AIP-mutated GH tumors > sporadic ones and NPG. Cavernous sinus invasion > non-invasive tumors. May have angiogenic effects. | [32, 50, 53] | 24; 27; 15 | Immunohistochemistry | 2020; 2019; 2019 |
| CD20 (B cells) | FPAs > NFPAs (especially GHomas). May have angiogenic effects. | [32, 52] | 24; 115 | Immunohistochemistry; RNA-seq. | 2020; 2020 |
| CD45 (lymphocytes) | The CD45 staining in pituitary adenomas was significantly greater than that in normal pituitary. There was no statistically significant difference among the various secretory types. High (MIB-1 > 3%) proliferative indices > low (MIB-1 ≤ 3%) proliferative indices. | [49, 54] | 48; 72 | Immunohistochemistry | 2016; 2010 |
| CD68 (macrophages) | The numbers of CD68+ cells showed a positive correlation with the tumor sizes and Knosp classification grades. Sparsely granulated GH and null cell tumors > densely granulated GH and ACTH tumors. AIP-mutated GH tumors > sporadic ones and NPG. The number of CD8+ lymphocytes was positively correlated with the number of CD68+ macrophages. Gonadotroph PitNETs present an increased CD68+ macrophage signature compared to somatotroph, lactotroph, and corticotroph PitNETs. The percentage of CD68+ and CD163+ infiltrating macrophages was significantly associated with the aggressiveness of gonadotropin tumors. Macrophages and NK cells are positively correlated. M2 macrophages > M1 macrophages. In the PA stroma, CD68+ macrophages > CD4+ T cells and CD8+ T cells. | [31, 41, 47, 48, 51–53] | 35; 134; 28;35; 64; 115; 15 | Immunohistochemistry; Computational approach; flow cytometry | 2021; 2020; 2020; 2015; 2020; 2020; 2019 |
| CD147 | Invasion tumors > non-invasive tumors. | [55] | 55 | Immunohistochemistry | 2005 |
| CD163 | The most abundant type of immune cell in PitNETs, and mainly CD163 +. | [14] | 45 | immunohistochemistry | 2019 |
| NK cells | Macrophages and NK cells are positively correlated. | [52] | 115 | Immunohistochemistry; RNA-seq. | 2020 |
| Neutrophils | PitNETs contained fewer neutrophils. NF-PitNETs had more neutrophils than somatotropinomas. | [14] | 45 | Immunohistochemistry | 2019 |
| CTLA-4 | There was no significant difference in CTLA-4 expression among tumor subtypes. | [52] | 115 | Immunohistochemistry; RNA-seq. | 2020 |
| PD-1 | NFPAs>FPAs (especially GHomas). High (MIB-1 > 3%) proliferative indices > low (MIB-1 ≤ 3%) proliferative indices. | [49, 52] | 48; 115 | Immunohistochemistry | 2016; 2020 |
| PD-L1 | FPAs > NFPAs (especially GHomas). Positively correlated with serum PRL and intratumoral immunostaining of PRL and GH. The score tended to be higher (p = 0.050) in the cavernous sinus invasion group. There was no difference between primary and recurrent adenomas. | [5, 42, 49, 50, 52, 56] | 67; 191; 48; 27; 115; 55. | Immunohistochemistry; RNA-seq. | 2020; 2018; 2016; 2019; 2020; 2020 |
Abbreviations: FPAs functional pituitary adenoma, NFPAs non-functional pituitary adenoma, GH growth hormone, PRL prolactin, ACTH adrenocorticotropic hormone, FoxP3 forkhead box protein P3, NK cell natural killer cell, PitNETs pituitary neuroendocrine tumor, NPG normal pituitary glands, AIP aryl hydrocarbon receptor-interacting protein, CTLA-4 co-inhibitory cytotoxic T lymphocyte-associated protein 4