在这篇综述中，我们探讨了甲状腺髓样癌（MTC）的潜在分子生物学及其与宿主免疫系统的相互作用。 MTC 始终由少数特定致病变异驱动，除此之外，肿瘤发生几乎不需要额外的遗传事件。这解释了与其他癌症相比，大多数 MTC 中肿瘤突变负担极低的原因。然而，由于肿瘤突变负荷（TMB）较低，因此呈递给宿主免疫系统的肿瘤相关新抗原的水平相应较低。这降低了肿瘤的可见性和抗肿瘤免疫反应的活力，并表明 MTC 免疫治疗的疗效可能很差，承认这一推论很大程度上是基于其他肿瘤类型数据的推断。特定 RET（转染期间重新排列）致病变异在 MTC 肿瘤发生中的主导地位合理化了靶向 RET 特异性酪氨酸激酶抑制剂 (TKI) 与多激酶抑制剂 (MKI) 相比所观察到的功效。通路抑制剂的治疗持久性是一个持续的研究焦点。它可能受到 TKI 治疗产生的选择压力的限制，促进耐药肿瘤细胞克隆的存活，这些克隆可以通过结合位点突变、激活替代途径以及调节肿瘤微环境 (TME) 的细胞和细胞因子环境来逃避途径抑制。

In this review, we explore the underlying molecular biology of medullary thyroid carcinoma (MTC) and its interplay with the host immune system. MTC is consistently driven by a small number of specific pathogenic variants, beyond which few additional genetic events are required for tumorigenesis. This explains the exceedingly low tumour mutational burden seen in most MTC, in contrast to other cancers. However, because of the low tumour mutational burden (TMB), there is a correspondingly low level of tumour-associated neoantigens that are presented to the host immune system. This reduces tumour visibility and vigour of the anti-tumour immune response and suggests the efficacy of immunotherapy in MTC is likely to be poor, acknowledging this inference is largely based on the extrapolation of data from other tumour types. The dominance of specific RET (REarranged during Transfection) pathogenic variants in MTC tumorigenesis rationalizes the observed efficacy of the targeted RET-specific tyrosine kinase inhibitors (TKIs) in comparison to multi-kinase inhibitors (MKIs). Therapeutic durability of pathway inhibitors is an ongoing research focus. It may be limited by the selection pressure TKI treatment creates, promoting survival of resistant tumour cell clones that can escape pathway inhibition through binding-site mutations, activation of alternate pathways, and modulation of the cellular and cytokine milieu of the tumour microenvironment (TME).