Vall d'Hebron University Hospital, Medical Oncology Department. Gastrointestinal and Endocrine Tumor Unit. Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Front Endocrinol (Lausanne). 2022 Aug 5;13:929091. doi: 10.3389/fendo.2022.929091. eCollection 2022.
Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in thyroid neoplasms. Programmed death-ligand 1 (PD-L1) staining by immunohistochemistry has shown higher expression in anaplastic thyroid cancer (ATC) compared to other subtypes. The tumor mutational burden in thyroid neoplasms is low but seems to be higher in ATC. Immune infiltrates in the tumor microenvironment (TME) differ between the different thyroid neoplasm subtypes. In general, differentiated thyroid cancer (DTC) has a higher number of tumor-associated lymphocytes and regulatory T cells (Tregs), while ATC and medullary thyroid cancer (MTC) display a high density of tumor-associated macrophages (TAMs). Nevertheless, results from clinical trials with immunotherapy as monotherapy or combinations have shown limited efficacy. Further investigation into new strategies aside from anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)/programmed death 1 (PD-1)/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in thyroid neoplasms is more than needed in the near future.
免疫疗法改变了晚期癌症患者的治疗方法，不同的 III 期临床试验显示出不同组织学类型的持久反应。这篇综述重点介绍了甲状腺肿瘤中免疫治疗反应和疗效的潜在预测生物标志物的临床前和临床证据。免疫组化检测程序性死亡配体 1（PD-L1）染色显示，间变性甲状腺癌（ATC）比其他亚型表达更高。甲状腺肿瘤的肿瘤突变负担较低，但 ATC 似乎更高。肿瘤微环境（TME）中的免疫浸润在不同的甲状腺肿瘤亚型之间存在差异。一般来说，分化型甲状腺癌（DTC）有更多的肿瘤相关淋巴细胞和调节性 T 细胞（Tregs），而 ATC 和甲状腺髓样癌（MTC）则显示出高密的肿瘤相关巨噬细胞（TAMs）。然而，免疫疗法作为单一疗法或联合疗法的临床试验结果显示疗效有限。除了抗细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）/程序性死亡 1（PD-1）/PD-L1 抗体之外，还需要进一步研究新的策略，验证预测生物标志物，并更好地选择甲状腺肿瘤临床试验的人群，这在不久的将来是非常必要的。
