The immune network in thyroid cancer

Abstract

The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

Keywords: Angiogenesis; CXCL8/IL-8; T reg cells; chemokines; dendritic cells; lymphangiogenesis; macrophages; mast cells; neutrophils; thyroid cancer.

Figure 1.

Hypothetical diagram depicting immune orchestration of tumor angiogenesis and lymphangiogenesis in TC. Immune cells infiltrating TCs can play two complementary roles at the same time. On one hand, several immune cells can modulate angiogenesis thus favoring tumor growth. On the other hand, TAMs and TAMCs, can play a dual role modulating not only angiogenesis but also lymphangiogenesis thus contributing to the formation of metastasis. The role of Tie2⁺ TEM, TAN and basophils (gray) in angiogenesis/lymphangiogenesis has been demonstrated in several human cancers and in chronic inflammatory disorders, but not yet in human TCs.

Figure 2.

Hypothetical scheme of immune network in TC. The immune network in thyroid cancer is a complex and dynamic system characterized by multiple interactions between tumor cells and a wide spectrum of immune cells. Tumor-infiltrating immune cells interact each other and with tumor cells in a complex synergistic and opposite manner still largely unknown. Several cytokines, chemokines, angiogenic and lymphangiogenic factors, derived from both immune cells and tumor cells, enrich the complexity of the inflammatory tumor microenvironment. The roles of Tie2⁺ TEM, NKT cells, TAN, Tfh cells, γδ T cells and Th9 cells (gray) have been demonstrated in several other human cancers or are under investigation in human TCs. Protumor or antitumor activities of Th17 and Tc17 cells are context dependent (dashed line).