The immune landscape of the microenvironment of thyroid cancer is closely related to differentiation status.

ABSTRACT

We have read with great interest the article entitled "Identification of an immune-related signature indicating the dedifferentiation of thyroid cells" by Wang et al. Their data reinforce our own previous results, here compiled. Anaplastic thyroid carcinoma had higher stromal scores, immune scores and enrichment of most immune cells than the control groups, suggesting that the immune microenvironment may correlate with differentiation status in thyroid cancer. We previously demonstrated that the differentiation status expressed by the pattern of protein expression may be related to the profile of immune cell infiltration of differentiated thyroid carcinoma. Wang et al. also explored the differences between the high-risk and low-risk score groups of samples. Among the distinct signaling pathways enriched in the high-risk score group, the epithelial to mesenchymal transition, TNFα signaling, and some common immune-related signaling pathways, including the IL-6/JAK/STAT3 pathway, interferon alpha response, interferon gamma response and inflammatory response were observed with high normalized enrichment score. We also investigated the IL-6 protein immune-histochemical expression in a retrospective study of 114 patients with papillary thyroid carcinoma and 39 patients with follicular thyroid carcinoma. We also obtained samples of 14 normal thyroid tissues from autopsies, 50 goiters and 43 follicular adenoma. We found IL-6 more frequently positive among malignant tumors than non-malignant samples. We demonstrated that IL-6 positivity was associated with infiltration of CD3 + cells, CD16 + cells and CD68 + macrophages. In addition, IL-6 expression was associated with infiltration of activated lymphocytes such as Granzyme B + cells and CD69 + cells. IL-6 positivity was not associated with infiltration of CD4+, CD8+, CD20+, FOXP3+, CD25 + cells but IL-6 was associated with tumor expression of PD-L1, FOXP3, IL-17, COX2, IL-1ß, IL-10, CD134, IL-23. In summary, Wang et al. beautiful data reinforce the seminal idea that the immune landscape is closely related to the differentiation status of the tumor. This concept may help select individuals who deserve more careful attention, an essential point in the management of patients with mostly indolent tumors such as those of the thyroid. In fact, our results, here compiled, were obtained with immune-histochemistry, a routine laboratory technique that offers the possibility of simpler and practical execution.