Diminished CD8A/FOXP3 Immune Ratio in Tall Cell Variant Predicts Recurrence-free Survival in Papillary Thyroid Carcinoma

Sunday, October 18, 2026

1:12 PM - 1:18 PM PT

Location: Theatre 411

Presenting Author(s)

DA

David Zachariah Allen, MD

Assistant Professor
New York Medical College
Hideout, UT, United States

Co-Author(s)

SB

Sydney Barish, n/a

Medical Student
Emory University School of Medicine
Atlanta, Georgia, United States
GD

Georges E. Daoud, MD

Resident
Emory University, Georgia, United States
CK

Celeste Kim, MD

Resident
Emory University, United States

Senior Author(s)

Merry E. Sebelik, MD, FACS, MAMSE

Professor
Emory University
Atlanta, GA, United States

Disclosure(s):

David Zachariah Allen, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Merry E. Sebelik, MD, FACS, MAMSE:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Tall cell variant (TCV) is a globally aggressive subtype of papillary thyroid carcinoma (PTC) with higher recurrence rates, however, its immune landscape remains poorly characterized despite its established molecular drivers. We hypothesized that TCV exhibits a more "exhausted" immune microenvironment, characterized by a lower ratio of cytotoxic T-cells (CD8A) to regulatory T-cells (FOXP3), and that this ratio predicts recurrence-free survival (RFS).

Methods: We analyzed transcriptomic and clinical data from the TCGA-THCA cohort (n=349). We first compared the CD8A/FOXP3 ratio between Classical papillary thyroid carcinoma (PTC) and tall cell variant (TCV). Recurrence-free survival (RFS) was then assessed using the ratio as both a continuous variable and an optimized binary threshold determined by maximally selected rank statistics. A multivariate Cox proportional hazards model was used to adjust for age and AJCC stage.

Results: Tall cell variant (TCV) exhibited a significantly lower CD8A/FOXP3 ratio compared to Classical PTC (p < 0.05), suggesting a more suppressive immune microenvironment in aggressive variants. When analyzing the entire cohort, the ratio as a continuous variable trended toward significance for RFS (HR 0.56, p = 0.06). However, an optimized threshold (-0.152) revealed a robust prognostic signal as patients in the "Immune-Exhausted" group had significantly worse RFS (p = 0.004). On multivariate analysis, this immune threshold was the only significant independent predictor of recurrence (HR 5.88; 95% CI 1.66-20.86; p = 0.006), while age (p = 0.31) and AJCC stage (p = 0.99) were not.

Conclusions: These findings demonstrate that TCV is characterized by an unfavorable immune profile which directly correlates with clinical failure. The CD8A/FOXP3 ratio serves as a potent, independent molecular marker for recurrence. Identifying this "Immune-Exhausted" phenotype may improve risk stratification beyond traditional staging and support the use of intensified surveillance or adjuvant therapies in high-risk patients.