Over the past few decades, understanding how tumor cells evade the immune system and their communication with their tumor microenvironment, has been the subject of intense investigation, with the aim of developing new cancer immunotherapies. The current therapies against cancer such as monoclonal antibodies against checkpoint inhibitors, adoptive T-cell transfer, cytokines, vaccines, and oncolytic viruses have managed to improve the clinical outcome of the patients. However, in some tumor entities, the response is limited and could benefit from the identification of novel therapeutic targets. It is known that tumor-extracellular matrix interplay and matrix remodeling are necessary for anti-tumor and pro-tumoral immune responses. Proteoglycans are dominant components of the extracellular matrix and are a highly heterogeneous group of proteins characterized by the covalent attachment of a specific linear carbohydrate chain of the glycosaminoglycan type. At cell surfaces, these molecules modulate the expression and activity of cytokines, chemokines, growth factors, adhesion molecules, and function as signaling co-receptors. By these mechanisms, proteoglycans influence the behavior of cancer cells and their microenvironment during the progression of solid tumors and hematopoietic malignancies. In this review, we discuss why cell surface proteoglycans are attractive pharmacological targets in cancer, and we present current and recent developments in cancer immunology and immunotherapy utilizing proteoglycan-targeted strategies.

在过去的几十年中，了解肿瘤细胞如何逃避免疫系统及其与肿瘤微环境的交流，一直是研究的热点，旨在开发新的癌症免疫疗法。当前针对癌症的疗法，例如针对检查点抑制剂的单克隆抗体，过继性T细胞转移，细胞因子，疫苗和溶瘤病毒，已设法改善了患者的临床疗效。然而，在某些肿瘤实体中，反应是有限的，并且可以受益于新治疗靶标的鉴定。已知肿瘤-细胞外基质相互作用和基质重塑对于抗肿瘤和促肿瘤免疫应答是必需的。蛋白聚糖是细胞外基质的主要成分，并且是蛋白质的高度异质性组，其特征在于糖胺聚糖类型的特定线性碳水化合物链的共价连接。在细胞表面，这些分子调节细胞因子，趋化因子，生长因子，粘附分子的表达和活性，并起信号共受体的作用。通过这些机制，蛋白聚糖在实体瘤和造血系统恶性肿瘤的发展过程中影响癌细胞的行为及其微环境。在这篇综述中，我们讨论了为什么细胞表面蛋白聚糖是癌症中有吸引力的药理学靶标，并且我们介绍了利用蛋白聚糖靶向策略的癌症免疫学和免疫疗法的当前和最新进展。