AB016. Different pattern of indoleamine 2,3-dioxygenase 1 (IDO1) and PD-L1 immunoexpression in thymomas

Background: Indoleamine 2,3-dioxygenase 1 (IDO1), a heme enzyme has been implicated in acquisition of peripheral immune tolerance in the tumor microenvironment as well as peripheral blood. It decreases antitumor response by suppressing T cell activation. Thymomas show strong expression of PD-L1 with highest positivity in type B thymomas. With increased advances in immunotherapy, expression of IDO1 in thymomas may have translational relevance and hence the need for this study. Methods: This was a retrospective study in a tertiary care center including 60 morphologically confirmed cases of thymoma. Tissue microarrays were prepared and immunohistochemistry was performed for PD-L1 (SP263) and IDO1 (V1NC3IDO). Cases with immunopositive aggregates of tumor or other cells (immune cells, mesenchymal cells, endothelial cells) (≥2/low power field) were considered as IDO1 positive. Immunostaining of >25% in the thymic epithelial cells was considered positive for PD-L1. The results were compared with clinical parameters and statistical analysis was performed. Results: Of 60 cases of thymoma, 27 (45%) showed IDO1 immunopositivity in the stromal endothelial cells, immune cells, fibroblasts, and tumor cells. IDO1 expression was observed in all the subtypes including 25% of type A, 53.49% of type B (B1/B2/B3) and 25% of type AB (P value =0.199). Most of the IDO1 positive cases did not have myasthenia gravis (MG) (77.78%) (P value =0.053). No significant association was observed between IDO1 positive tumors and clinical parameters like age, sex and Masaoka Koga stage. PD-L1 immunopositivity showed significant association with type B thymomas (P value =0.001). Conclusions: IDO1 is expressed in a substantial number of thymomas and show maximum expression in type B thymomas similar to PD-L1. Although immunoreactivity of PD-L1 and IDO1 is seen in different types of cells, both showed maximum expression in type B thymomas. PD-L1 is expressed mostly by thymic epithelial cells whereas IDO1 mostly stains peritumoral stromal endothelial cells, immune cells, and mesenchymal cells. It is possible that the PD-L1-IDO1 axis plays an important role in immune regulation and pathogenesis of thymic epithelial tumors which can be explored in further studies.