Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
German Translational Cancer Consortium (DKTK), Heidelberg, Germany.
Br J Cancer. 2019 Apr;120(9):871-882. doi: 10.1038/s41416-019-0441-6. Epub 2019 Apr 2.
Significant progress in the development of new immunotherapies has led to successful clinical trials for malignant melanoma and non-small cell lung cancer; however, for the majority of solid tumours of the gastrointestinal tract, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells, and interactions between the tumour cells and all other cells in the local microenvironment of solid tumours. A large fraction of immune cells present in and around solid tumours derive from the innate arm of the immune system and using these cells against tumours offers an alternative immunotherapeutic option, especially as current strategies largely harness the adaptive arm of the immune system. This option is currently being investigated and attempts at using the innate immune system for gastrointestinal cancers are showing initial results. Several important factors, including cytokines, chemotherapeutics and the microbiome, influence the plasticity and functionality of innate (myeloid) cells in the microenvironment, and this complexity of regulation has limited translation into successful trials so far. In this review, current concepts of the immunobiology of the innate arm in the tumour microenvironment are presented in the context of clinical translation.
新的免疫疗法在恶性黑色素瘤和非小细胞肺癌的临床试验中取得了显著进展；然而，对于胃肠道的大多数实体瘤，几乎没有或没有看到进展。免疫疗法的疗效受到一系列复杂的免疫细胞的影响，以及肿瘤细胞与实体瘤局部微环境中所有其他细胞之间的相互作用的影响。存在于实体瘤内部和周围的大量免疫细胞来源于免疫系统的固有部分，利用这些细胞对抗肿瘤提供了另一种免疫治疗选择，特别是因为目前的策略主要利用免疫系统的适应性部分。目前正在对此进行研究，并且使用固有免疫系统治疗胃肠道癌的尝试正在取得初步结果。几个重要因素，包括细胞因子、化疗药物和微生物组，影响微环境中固有（髓样）细胞的可塑性和功能，到目前为止，这种调节的复杂性限制了其转化为成功的试验。在这篇综述中，根据临床转化的背景，介绍了肿瘤微环境中固有免疫的免疫生物学的当前概念。
