Pramil Elodie, Dillard Clémentine, Escargueil Alexandre E
Sorbonne Université, INSERM U938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
Alliance Pour la Recherche en Cancérologie-APREC, Tenon Hospital, F-75012 Paris, France.
Cancers (Basel). 2021 Apr 4;13(7):1713. doi: 10.3390/cancers13071713.
Immunotherapy is a very promising field of research and application for treating cancers, in particular for those that are resistant to chemotherapeutics. Immunotherapy aims at enhancing immune cell activation to increase tumor cells recognition and killing. However, some specific cancer types, such as colorectal cancer (CRC), are less responsive than others to the current immunotherapies. Intrinsic resistance can be mediated by the development of an immuno-suppressive environment in CRC. The mutational status of cancer cells also plays a role in this process. CRC can indeed be distinguished in two main subtypes. Microsatellite instable (MSI) tumors show a hyper-mutable phenotype caused by the deficiency of the DNA mismatch repair machinery (MMR) while microsatellite stable (MSS) tumors show a comparatively more "stable" mutational phenotype. Several studies demonstrated that MSI CRC generally display good prognoses for patients and immunotherapy is considered as a therapeutic option for this type of tumors. On the contrary, MSS metastatic CRC usually presents a worse prognosis and is not responsive to immunotherapy. According to this, developing new and innovative models for studying CRC response towards immune targeted therapies has become essential in the last years. Herein, we review the in vitro and in vivo models used for research in the field of immunotherapy applied to colorectal cancer.
免疫疗法是治疗癌症非常有前景的研究和应用领域，尤其适用于那些对化疗耐药的癌症。免疫疗法旨在增强免疫细胞的激活，以增加对肿瘤细胞的识别和杀伤。然而，某些特定的癌症类型，如结直肠癌（CRC），对当前的免疫疗法反应不如其他癌症。CRC内在抗性可由免疫抑制环境的形成介导。癌细胞的突变状态在这一过程中也起作用。CRC确实可分为两种主要亚型。微卫星不稳定（MSI）肿瘤表现出由于DNA错配修复机制（MMR）缺陷导致的高突变表型，而微卫星稳定（MSS）肿瘤表现出相对更“稳定”的突变表型。多项研究表明，MSI CRC患者通常预后良好，免疫疗法被认为是这类肿瘤的一种治疗选择。相反，MSS转移性CRC通常预后较差，对免疫疗法无反应。据此，近年来开发新的创新模型来研究CRC对免疫靶向治疗的反应变得至关重要。在此，我们综述了用于结直肠癌免疫治疗领域研究的体外和体内模型。
