In thyroid cancer, the tumor immune microenvironment (TIME) plays a crucial role in cancer development, progression and response to treatment. Like many other cancers, thyroid cancer creates a complex network of interactions with immune cells directly (cell-to-cell) and via humoral mediators (i.e., cytokines). This dynamic microenvironment undergoes constant modification, which can lead to changes in the immunophenotype that might explain cancer progression, dedifferentiation and resistance to treatment. According to the cancer immunoediting hypothesis, cancerous tumors can shape their immune microenvironment to create an immunosuppressive milieu that allows them to evade classic immune surveillance. One mechanism by which this occurs is through the reprogramming of immune cells, often shifting their phenotypes from cytotoxic to regulatory. Recent research has shed light on cellular components and molecular interactions within the thyroid cancer TIME. Immune cells such as Tumor-Associated Lymphocytes (TALs), myeloid-derived suppressor cells (MDSCs), Tumor-Associated Macrophages (TAMs) and Double-Negative (DN) T cells seem to play key roles in shaping the immune response to thyroid cancer. Additionally, cytokines, chemokines and other signaling molecules contribute to the communication and regulation of immune cells within that microenvironment. By studying these interactions, researchers aim to uncover not just potential therapeutic targets but also biomarkers of thyroid cancer that could provide clues on severity and progression. Based on that knowledge, strategies such as the use of immune checkpoint inhibitors, antigen-specific targeted immunotherapies, and immunomodulatory agents are being explored to enhance the anti-tumor immune response and overcome cancer immunosuppressive mechanisms. In this review, we analyze the available literature and provide our own experience to unravel the complexity of the thyroid immune microenvironment. Continued research in this area holds promise for improving outcomes through the identification of immune markers of severity/progression of thyroid cancer and the development of innovative immunotherapeutic approaches.
在甲状腺癌中，肿瘤免疫微环境（TIME）对癌症的发生发展及治疗反应起着至关重要的作用。与许多其他癌症类似，甲状腺癌通过直接（细胞间接触）和体液介质（如细胞因子）与免疫细胞形成复杂的相互作用网络。这一动态微环境持续发生改变，可能导致免疫表型的变化，从而解释癌症进展、去分化及治疗耐药等现象。根据癌症免疫编辑假说，肿瘤能够塑造其免疫微环境，形成免疫抑制状态以逃避免疫监视。其机制之一是通过免疫细胞的重编程，通常将其表型从细胞毒性转变为调节性。 近期研究揭示了甲状腺癌TIME中的细胞成分与分子相互作用。肿瘤相关淋巴细胞（TALs）、髓源性抑制细胞（MDSCs）、肿瘤相关巨噬细胞（TAMs）及双阴性（DN）T细胞等免疫细胞在塑造针对甲状腺癌的免疫应答中发挥关键作用。此外，细胞因子、趋化因子及其他信号分子参与该微环境中免疫细胞的通讯与调控。通过研究这些相互作用，研究者不仅旨在发掘潜在治疗靶点，更希望找到能够提示甲状腺癌严重程度与进展的生物标志物。 基于现有认知，诸如免疫检查点抑制剂、抗原特异性靶向免疫疗法及免疫调节剂等策略正在被探索，以增强抗肿瘤免疫应答并克服癌症免疫抑制机制。本文通过综合分析现有文献并结合自身研究经验，系统阐释甲状腺免疫微环境的复杂性。该领域的持续研究有望通过识别甲状腺癌严重程度/进展的免疫标志物及开发创新免疫治疗方法，最终改善临床预后。
Thyroid Cancer—The Tumor Immune Microenvironment (TIME) over Time and Space
肿瘤(癌症)患者之家