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. 2023 Apr 15;24(8):7314.
doi: 10.3390/ijms24087314.

IDO1 Protein Is Expressed in Diagnostic Biopsies from Both Follicular and Transformed Follicular Patients

Marie Beck Hairing Enemark  1   2 , Emma Frasez Sørensen  1 , Trine Engelbrecht Hybel  1   2 , Maja Dam Andersen  1   2 , Charlotte Madsen  1 , Kristina Lystlund Lauridsen  3 , Bent Honoré  4 , Francesco d'Amore  1 , Trine Lindhardt Plesner  5 , Stephen Jacques Hamilton-Dutoit  3 , Maja Ludvigsen  1   2
Affiliations

IDO1 Protein Is Expressed in Diagnostic Biopsies from Both Follicular and Transformed Follicular Patients

Marie Beck Hairing Enemark et al. Int J Mol Sci. .

Abstract

Follicular lymphoma (FL) is a lymphoid neoplasia characterized by an indolent clinical nature. Despite generally favorable prognoses, early progression and histological transformation (HT) to a more aggressive lymphoma histology remain the leading causes of death among FL patients. To provide a basis for possible novel treatment options, we set out to evaluate the expression levels of indoleamine 2,3-dioxygenase 1 (IDO1), an immunoinhibitory checkpoint molecule, in follicular and transformed follicular biopsies. The expression levels of IDO1 were assessed using immunohistochemical staining and digital image analysis in lymphoma biopsies from 33 FL patients without subsequent HT (non-transforming FL, nt-FL) and 20 patients with subsequent HT (subsequently transforming FL, st-FL) as well as in paired high-grade biopsies from the time of HT (transformed FL, tFL). Despite no statistical difference in IDO1 expression levels seen between the groups, all diagnostic and transformed lymphomas exhibited positive expression, indicating its possible role in novel treatment regimens. In addition, IDO1 expression revealed a positive correlation with another immune checkpoint inhibitor, namely programmed death 1 (PD-1). In summary, we report IDO1 expression in all cases of FL and tFL, which provides the grounds for future investigations of anti-IDO1 therapy as a possible treatment for FL patients.

Keywords: follicular lymphoma; histological transformation; indoleamine 2,3-dioxygenase.

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Conflict of interest statement

B.H. holds shares from Novo Nordisk A/S and Genmab A/S. Novo Nordisk A/S and Genmab A/S had no influence on the study design, analyses, and reporting of the results. All authors declare no relevant competing financial interests.

Figures

Figure 1
Figure 1
Intratumoral expression of IDO1 in FL. (A) Representative images of immunohistochemical staining of IDO1 in diagnostic nt-FL biopsies. Left: magnification of ×5, right: magnification of ×10. (B) Boxplot showing AFs of IDO1 in nt-FL, st-FL, and tFL samples, respectively. (C–E) Kaplan–Meier curves showing survival stratified according to IDO1 status and OS, PFS, and TFS, respectively. AF, area fraction; IDO1, indoleamine 2,3-dioxygenase 1; nt-FL, non-transforming FL; OS, overall survival; PFS, progression-free survival; st-FL, subsequently transforming FL; tFL, transformed FL; TFS, transformation-free survival.
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