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. 2022 Jul 18:12:871792.
doi: 10.3389/fonc.2022.871792. eCollection 2022.

Indoleamine 2,3-Dioxygenase Immune Status as a Potential Biomarker of Radioiodine Efficacy for Advanced Distant Metastatic Differentiated Thyroid Cancer

Liang Shi  1 , Rui Duan  1   2 , Qiong Jia  3 , Wenyu Wu  1 , Jianming Zhou  4 , Shaohua Li  1 , Hao Zhang  5 , Xue Xue  1
Affiliations

Indoleamine 2,3-Dioxygenase Immune Status as a Potential Biomarker of Radioiodine Efficacy for Advanced Distant Metastatic Differentiated Thyroid Cancer

Liang Shi et al. Front Oncol. .

Abstract

Purpose: Host immunity influences the impact of cancer therapy but the effect of immune status in radioiodine (RAI)-treated differentiated thyroid cancer (DTC) remains obscure. Here we investigated indoleamine 2,3-dioxygenase (IDO) activity as a biomarker of response to RAI in patients with distant metastatic DTC (dmDTC).

Methods: Patients with dmDTC receiving RAI were evaluated for serum IDO activity (kynurenine and kynurenine:tryptophan ratio) at baseline and 3 months after RAI. The optimal cut-off value for these biomarkers to predict response was established by receiver operating characteristic analysis. The relationship between disease outcomes, overall survival (OS) and progression-free survival (PFS), and IDO activity levels was studied.

Results: Higher baseline kynurenine:tryptophan ratio (>2.46) was correlated with poorer RAI response as well as shorter median PFS (45 mo versus not reached, p=0.002) and OS (78 mo versus not reached, p=0.035). High baseline kynurenine:tryptophan ratio was also correlated with a reduced number of tumor-infiltrating lymphocytes. Higher post/pre-kynurenine ratio (>1.69) was associated with survival endpoints: shorter median PFS (48 mo versus not reached, p=0.002) and OS (68 mo versus not reached, p=0.010). Favorable baseline and favorable change corresponded with better PFS and OS.

Conclusions: Our results suggest that RAI also alters IDO activity in dmDTC patients. IDO activity could predict progression and survival outcomes for advanced dmDTC patients. Serum IDO biomarker levels could be used to select dmDTC likely to benefit from RAI therapy, although further studies are necessary.

Keywords: 3-dioxygenase (IDO); differentiated thyroid cancer; immune suppression; indoleamine 2; predictive factors; radioiodine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers XW and JZ declared a shared affiliation with the authors to the handling editor at the time of review.

Figures

Figure 1
Figure 1
Changes of kynurenine concentrations (A) and the K/T ratios [Kynurenine (μM)/Tryptophan(μM) x 102] (B) in serum samples at pre-RAI and post-RAI time points.
Figure 2
Figure 2
Pre-RAI K/T ratio and treatment outcomes. (A) the pre-RAI K/T ratio according to the response to RAI treatment (B) ROC curve for pre-RAI K/T ratio in dmDTC patients (C) association of baseline K/T ratio with the number of CD3+ TILs (D) association of baseline K/T ratio with the number of CD8+ TILs (E) PFS curves of the dmDTC patients according to pre-RAI K/T ratio (F) OS curves of the dmDTC patients according to pre-RAI K/T ratio.
Figure 3
Figure 3
Post/pre-kynurenine ratio and treatment outcomes. (A) the post/pre-kynurenine according to the response to RAI treatment (B) ROC curve for post/pre-kynurenine in dmDTC patients (C) PFS curves of the dmDTC patients according to post/pre-kynurenine (D) OS curves of the dmDTC patients according to post/pre-kynurenine.
Figure 4
Figure 4
Combined effects of baseline Change of IDO on DTC tumor progression (A) and overall survival (B). Group 1: patients with low baseline K/T ratio and low post/pre-kynurenine ratio; Group 2 patients with high baseline K/T ratio and low post/baseline kynurenine ratio; Group 3: patients with low baseline K/T ratio and high post/baseline kynurenine ratio; Group 4: patients with high baseline K/T ratio and high post/baseline kynurenine ratio.
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