Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, WIMR 4031, Madison, WI, 53705, USA.
J Immunother Cancer. 2018 Jul 3;6(1):65. doi: 10.1186/s40425-018-0376-0.
Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy.
近年来，我们对细胞串扰动力学的理解取得了进展，这凸显了可以利用免疫疗法利用的宿主与肿瘤效应的重要性。肿瘤利用免疫检查点逃避适应性免疫反应。在过去十年中，随着免疫检查点抑制剂 (ICIs) 的发展，针对细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1) 或其配体（如 PD1 配体 1 (PD-L1)）的单克隆抗体的癌症免疫疗法发生了革命性变化。据报道，ICIs 对多种肿瘤类型具有活性，包括实体器官和血液恶性肿瘤。然而，不到三分之一的患者实现了持久且有意义的治疗反应。免疫检查点配体（例如 PD-L1）的表达、突变负担和肿瘤浸润淋巴细胞目前被用作预测对 ICI 反应的生物标志物。然而，它们并不能可靠地预测哪些患者将从这些治疗中受益。迫切需要发现新的生物标志物来预测治疗效果，并确定开发联合策略以提高反应率的领域。新出现的证据表明肿瘤细胞外基质 (ECM) 成分及其蛋白水解重塑产物在调节癌症免疫周期的每个步骤中都起着关键作用。在这里，我们回顾了肿瘤基质动力学和基质重塑在抗肿瘤免疫反应和免疫治疗中的作用，并提出了探索基于基质的生物标志物以确定免疫治疗候选者的建议。
