Immunopathology and Cancer Biomarkers Units, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, PN, Italy.
Head and Neck Cancer Medical Oncology 3 Department, Fondazione IRCCS Istituto Nazionale dei Tumori (INT) di Milano, Milan, Italy.
Crit Rev Oncol Hematol. 2022 Jul;175:103707. doi: 10.1016/j.critrevonc.2022.103707. Epub 2022 May 13.
Amongst the chief targets of immune-checkpoint inhibitors (ICIs), namely the Programmed cell death protein 1 (PD-1)/PD-Ligands (Ls) axis, most research has focused on PD-L1, while to date PD-L2 is still under-investigated. However, emerging data support PD-L2 relevant expression in malignancies of the head and neck area, mostly in head and neck squamous cell carcinoma (HNSCC) and salivary gland cancers (SGCs). In this context, ICIs have achieved highly heterogeneous outcomes, emphasizing an urgent need for the identification of predictive biomarkers. With the present review, we aimed at describing PD-L2 biological significance by focusing on its tissue expression, its binding to PD-1 and RGMb receptors, and its impact on physiological and anti-cancer immune response. Specifically, we reported PD-L2 expression rates and significant clinical correlates among different head and neck cancer histotypes. Finally, we described the biology of soluble PD-L2 form and its potential application as a prognostic and/or predictive circulating biomarker.
在免疫检查点抑制剂（ICI）的主要靶点中，即程序性细胞死亡蛋白 1（PD-1）/PD-配体（Ls）轴，大多数研究都集中在 PD-L1 上，而迄今为止 PD-L2 仍研究不足。然而，新出现的数据支持 PD-L2 在头颈部恶性肿瘤中表达相关，主要在头颈部鳞状细胞癌（HNSCC）和唾液腺癌（SGCs）中。在这种情况下，ICI 取得了高度异质性的结果，强调迫切需要确定预测性生物标志物。在本综述中，我们旨在通过关注其组织表达、与 PD-1 和 RGMb 受体的结合以及对生理和抗癌免疫反应的影响，来描述 PD-L2 的生物学意义。具体而言，我们报告了不同头颈部癌症组织类型中 PD-L2 的表达率和显著的临床相关性。最后，我们描述了可溶性 PD-L2 形式的生物学及其作为预后和/或预测性循环生物标志物的潜在应用。
