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. 2024 Mar 31;12(4):772.
doi: 10.3390/biomedicines12040772.

PD-L1 Expression in Neoplastic and Immune Cells of Thymic Epithelial Tumors: Correlations with Disease Characteristics and HDAC Expression

Ioanna E Stergiou  1   2 , Kostas Palamaris  2 , Georgia Levidou  3 , Maria Tzimou  2 , Stavros P Papadakos  2 , Georgios Mandrakis  2 , Christos Masaoutis  2 , Dimitra Rontogianni  4 , Stamatios Theocharis  2
Affiliations

PD-L1 Expression in Neoplastic and Immune Cells of Thymic Epithelial Tumors: Correlations with Disease Characteristics and HDAC Expression

Ioanna E Stergiou et al. Biomedicines. .

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression.

Methods: Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6.

Results: The PD-L1 tumor proportion score (TPS) was higher, while the immune cell score (IC-score) was lower in the more aggressive TET subtypes and in more advanced Masaoka-Koga stages. A positive correlation between PD-L1 and HDAC-3, -4, and -5 cytoplasmic expression was identified.

Conclusions: Higher PD-L1 expression in neoplastic cells and lower PD-L1 expression in immune cells of TETs characterizes more aggressive and advanced neoplasms. Correlations between PD-L1 and HDAC expression unravel the impact of epigenetic regulation on the expression of immune checkpoint molecules in TETs, with possible future applications in combined therapeutic targeting.

Keywords: HDAC; PD-L1; thymic epithelial tumors; thymoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunohistochemical expression of PD-L1 with SP263 in different TET subtypes. (A) TET subtype A, (B) TET subtype B2, (C) TET subtype B3 (Magnification ×40).
Figure 2
Figure 2
Schematic representation of the association between PD-L1 (SP263) TPS and WHO TET subtypes (left panel), as well as Masaoka–Koga stage (right panel). Dots represent outliers. TC, thymic carcinoma; TETs, thymic epithelial tumors.
Figure 3
Figure 3
Schematic representation of the distributions of various PD-L1 (SP263) IC-score categories among WHO TET subtypes (left panel), as well as Masaoka–Koga stage (right panel). IC-score, immune cell score; TC, thymic carcinoma; TETs, thymic epithelial tumors.
Figure 4
Figure 4
Immunohistochemical expression of PD-L1 with SP142 in different TET subtypes. (A) TET subtype A, (B) TET subtype B2, (C) TET subtype B3 (Magnification ×40).
Figure 5
Figure 5
Schematic representation of the association between PD-L1 (SP142) TPS and WHO TET subtypes (left panel), as well as Masaoka–Koga stage (right panel). Dots represent outliers. TC, thymic carcinoma; TETs, thymic epithelial tumors.
Figure 6
Figure 6
Schematic representation of the distributions of various PD-L1 (SP142) IC-score categories among WHO TET subtypes (left panel), as well as Masaoka–Koga stage (right panel). IC-score, immune cell score; TC, thymic carcinoma; TETs, thymic epithelial tumors.
See this image and copyright information in PMC

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