Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer

Context: Ten to 30% of patients with papillary thyroid cancer (PTC) develop recurrent disease and may benefit from innovative adjuvant therapies. Immune-based therapies are under investigation to treat many types of cancer. The role of the immune system in PTC is poorly understood. Objective: We investigated whether tumor-associated lymphocytes (TAL), in the absence of background thyroiditis (LT), contribute to disease severity. We hypothesized that the type of lymphocytes associated with PTC would correlate with parameters of disease. Design: This retrospective study analyzed archived PTC samples for the presence of TAL and/or LT. A group of patients with TAL was evaluated for lymphocyte subsets by immunohistofluorescence. Patients and Setting: One hundred PTC patients were analyzed for LT and TAL, and 10 PTC patients with TAL were assessed for lymphocyte subsets at University of Colorado Hospital. Main Outcome: We assessed correlations between disease and the presence of TAL, LT, and lymphocyte subset frequency. Results: Patients with TAL exhibited higher disease stage and increased incidence of invasion and lymph node metastasis compared with patients without lymphocytes or with LT. CD4(+) T cell frequency correlated with tumor size (r = 0.742; P = 0.017). FoxP3(+) regulatory T cell (Treg) frequency correlated with lymph node metastases (r = 0.858; P = 0.002), and CD8 to Treg ratio correlated inversely with tumor size (r = -0.804; P = 0.007). Conclusions: TAL and high Treg frequency in primary thyroid tumors correlates with more aggressive disease. Future prospective studies may identify Treg frequency as a predictive factor in PTC, and the suppressive effects of Treg should be considered in the design of immune-based therapies. (J Clin Endocrinol Metab 95: 2325-2333, 2010)