Tumor-Infiltrating Lymphocytes as Mediators of the Obesity and Papillary Thyroid Carcinoma Lymph Node Metastasis Association: An Observational Retrospective Cohort Study

Obesity increases the risk of papillary thyroid carcinoma (PTC) and lymph node metastasis (LNM), possibly via modulation of the tumor immunological microenvironment.

The STROCSS guideline was followed to conduct a retrospective cohort study. Binary logistic regression analysis with odds ratios (OR) was performed to assess the association between tumor-infiltrating lymphocytes (TILs), obesity, and LNM. Using The Cancer Genome Atlas (TCGA) data, we examined the relationship between immune cell subsets and obesity-regulating molecules in thyroid cancer tissues. The Cox regression risk model was used to analyze the prognosis of thyroid cancer.

After adjusting for confounding factors, our findings revealed that overweight and obesity were associated with a decrease in TIL infiltration (OR 0.876, p = 0.005 and OR 0.795, p = 0.001, respectively). Furthermore, these conditions were observed to be correlated with increased likelihood of LNM (OR 1.134, p = 0.005 and OR 1.307, p < 0.001, respectively). On the contrary, TIL infiltration was inversely associated with LNM (OR 0.868, p < 0.001). When controlling for TIL infiltration as the sole variable, the combination of obesity and TIL infiltration did not independently predict LNM (adjusted OR 1.442, p = 0.113). However, obesity alone was found to elevate the likelihood of LNM (adjusted OR 1.539, p = 0.02). Additionally, adiponectin (a crucial adipokine) was reduced in obesity and demonstrated a negative correlation with the abundance of infiltrated dendritic cells and regulatory T cells, as evidenced by TCGA data analysis. Furthermore, ADIPOR2 expression negatively correlated with LNM and positively associated with unfavorable prognosis in PTC, with a hazard ratio of 0.480 (p = 0.007).

TIL infiltration may affect obesity-associated PTC LNM. Obesity may affect LNM and result in poor prognosis through ADIPOR2 regulation of antitumor immune cells.