Medical Oncology and Translational Research, S. Croce & Carle Teaching Hospital, Cuneo.
Candiolo Cancer Center - FPO, Candiolo (Turin), Italy.
Curr Opin Oncol. 2020 May;32(3):203-209. doi: 10.1097/CCO.0000000000000623.
The aim of this review is to describe the major steps leading to the immunosuppressive tumor microenvironment and to summarize some of the new immunotherapies that interfere with these mechanisms.
Immunotherapy has improved the outcome of relapsed/metastatic head and neck squamous cell carcinoma (HNSCC). However, most patients still do not respond to treatment and median overall survival remains short with a modest rate of long-term survivors. There is a growing awareness that tumor immune-escape is a complex process that involves many redundant mechanisms other than immune check-points. They interfere with the innate immune response, activation of adaptive immune response, homing of effector T cells, their clonal expansion, viability, and efficiency. This abundance of immunosuppressive mechanisms explains the limited results achieved by immune checkpoint inhibitors. Combined treatments targeting different mechanisms of escape are in development to further improve the outcome of patients with HNSCC.
Many mechanisms favor tumor immune-escape. Each tumor exploits preferably some of them and the challenge is to understand which are the best targets in each tumor. This knowledge is an important tool to design future combination strategies based on strong biological rationales, which could offer better results than simple empirical combinations.
本文旨在描述导致免疫抑制肿瘤微环境的主要步骤，并总结一些干扰这些机制的新免疫疗法。
免疫疗法改善了复发性/转移性头颈部鳞状细胞癌（HNSCC）的预后。然而，大多数患者仍对治疗无反应，中位总生存期仍然较短，长期幸存者的比例也较低。人们越来越意识到，肿瘤免疫逃逸是一个复杂的过程，涉及许多除免疫检查点以外的冗余机制。它们干扰先天免疫反应、适应性免疫反应的激活、效应 T 细胞的归巢、它们的克隆扩增、活力和效率。这种丰富的免疫抑制机制解释了免疫检查点抑制剂所取得的有限效果。目前正在开发针对逃逸不同机制的联合治疗方法，以进一步改善 HNSCC 患者的预后。
许多机制有利于肿瘤免疫逃逸。每个肿瘤都优先利用其中的一些机制，挑战在于了解在每个肿瘤中哪些是最佳靶点。这些知识是设计基于强大生物学原理的未来联合策略的重要工具，这些策略可能比简单的经验性组合提供更好的结果。
