Immune Escape Mechanism is Impaired in the Microenvironment of Thyroid Lymph Node Metastasis

Abstract

We previously identified the infiltration of CD8+ lymphocytes and COX2 expression as an independent factor of risk for recurrence in papillary thyroid carcinoma (PTC) patients. However, the presence of lymph node (LN) metastasis at diagnosis lost its significance in a multivariate model analysis. These results encouraged us to compare the immune cells arrangement in the microenvironment of the LN metastasis and the primary tumor. We studied 104 consecutive PTC patients. Tissue specimens of both primary tumor and LN metastasis at the time of diagnosis were available in 19 out of them. These 19 patients were followed up for 32 to 81 months (64.7 ± 47.5 months). Immune cell markers were investigated using immunohistochemistry and included tumor infiltrating lymphocytes subsets such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69, and CD25. We also investigated the expression of COX2 in tumor cells. Paired t test showed an increase of GRANZYME-B+ lymphocytes density in LN metastasis compared to the corresponding primary tumor, suggesting that LN metastasis is enriched with activated immune cells. In addition, we observed a decrease in COX2 expression levels in LN metastasis compared to the corresponding primary tumors, reinforcing the idea that the immune escape mechanism is impaired in the microenvironment of thyroid LN metastasis. In conclusion, our data demonstrated that the microenvironment of PTC LN metastasis present features that favor an anti-tumor immune response. This may help to explain why the presence of LN metastasis at diagnosis is not a good predictor of PTC patients' survival or disease progression.

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