The role of the inflammatory microenvironment in thyroid carcinogenesis

Abstract

Immune responses against thyroid carcinomas have long been demonstrated and associations between inflammatory microenvironment and thyroid carcinomas repeatedly reported. This scenario has prompted scientists throughout the world to unveil how the inflammatory microenvironment is established in thyroid tumors and what is its influence on the outcome of patients with thyroid carcinoma. Many studies have reported the role of evasion from the immune system in tumor progression and reinforced the weakness of the innate immune response toward thyroid cancer spread in advanced stages. Translational studies have provided evidence that an increased density of tumor-associated macrophages in poorly differentiated thyroid carcinoma (DTC) is associated with an aggressive phenotype at diagnosis and decreased cancer-related survival, whereas well-DTC microenvironment enriched with macrophages is correlated with improved disease-free survival. It is possible that these different results are related to different microenvironments. Several studies have provided evidence that patients whose tumors are not infiltrated by lymphocytes present a high recurrence rate, suggesting that the presence of lymphocytes in the tumor microenvironment may favor the prognosis of patients with thyroid carcinoma. However, the effect of lymphocytes and other immune cells on patient outcome seems to result from complex interactions between the tumor and immune system, and the molecular pattern of cytokines and chemokines helps to explain the involvement of the immune system in thyroid tumor progression. The inflammatory microenvironment may help to characterize aggressive tumors and to identify patients who would benefit from a more invasive approach, probably sparing the vast majority of patients with an indolent disease from unnecessary procedures.

The immune network in thyroid cancer

“…Cytokines play a role in the pathogenesis of autoimmune thyroid disease and contribute to several aspects of TC initiation and growth. 4 IL-1 promotes tumor growth through the induction of prometastatic genes (e.g., matrix metalloproteinases), angiogenic molecules (VEGF, CXCL8/IL-8, etc.) and cytokines (IL-6, TNF-a, and TGF-b).…”

“…Indeed, a mixture of immune cells and mediators has been described in TC, associated with tumor progression and patient clinical outcome. 4 The purpose of this review is to discuss recent findings investigating how the immune system can affect TC development and progression and its influence on patient clinical outcome.…”

Preoperative High Neutrophil-Lymphocyte Ratio May Be Associated with Lateral Lymph Node Metastasis in Patients with Papillary Thyroid Cancers

“…31) Consequently, lymphocytic infiltration in PTC may have protective effects and the loss of protective effects in poorly differentiated or anaplastic thyroid carcinoma may contribute to aggressive behavior and poor prognostic outcomes. [29][30][31] This study has some limitations. First, our study was of retrospective design and 43 patients without available preoperative blood cell counts were excluded.…”

“…29,30) Meanwhile, intratumoral lymphocytic infiltration was intensely reduced or absent in poorly differentiated or undifferentiated thyroid carcinoma. 31) Consequently, lymphocytic infiltration in PTC may have protective effects and the loss of protective effects in poorly differentiated or anaplastic thyroid carcinoma may contribute to aggressive behavior and poor prognostic outcomes.…”

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

“…Some tumors evade immunosurveillance, which can occur through an inhibition of T-cell function induced by the expression of molecules such as CTLA-4, PD-1, or PD-L1 (43,44). Treatment with antibodies directed against checkpoint inhibitors (e.g., PD-1/PD-L1) has shown promise in other cancer types and is being investigated in advanced RAI-refractory thyroid cancer, used either alone or in combination with an MKI or an RAI (5,45).…”