Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
Servicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014, Granada, Spain.
Cancer Metastasis Rev. 2021 Jun;40(2):501-517. doi: 10.1007/s10555-021-09964-4. Epub 2021 Apr 15.
In recent years, immunotherapy has proven to be an effective treatment against cancer. Cytotoxic T lymphocytes perform an important role in this anti-tumor immune response, recognizing cancer cells as foreign, through the presentation of tumor antigens by MHC class I molecules. However, tumors and metastases develop escape mechanisms for evading this immunosurveillance and may lose the expression of these polymorphic molecules to become invisible to cytotoxic T lymphocytes. In other situations, they may maintain MHC class I expression and promote immunosuppression of cytotoxic T lymphocytes. Therefore, the analysis of the expression of MHC class I molecules in tumors and metastases is important to elucidate these escape mechanisms. Moreover, it is necessary to determine the molecular mechanisms involved in these alterations to reverse them and recover the expression of MHC class I molecules on tumor cells. This review discusses the role and regulation of MHC class I expression in tumor progression. We focus on altered MHC class I phenotypes present in tumors and metastases, as well as the molecular mechanisms responsible for MHC-I alterations, emphasizing the mechanisms of recovery of the MHC class I molecules expression on cancer cells. The individualized study of the HLA class I phenotype of the tumor and the metastases of each patient will allow choosing the most appropriate immunotherapy treatment based on a personalized medicine.
近年来，免疫疗法已被证明是对抗癌症的一种有效治疗方法。细胞毒性 T 淋巴细胞在这种抗肿瘤免疫反应中发挥重要作用，通过 MHC Ⅰ类分子呈递肿瘤抗原，将癌细胞识别为异己。然而，肿瘤和转移灶会发展出逃避这种免疫监视的机制，可能会失去这些多态性分子的表达，从而使细胞毒性 T 淋巴细胞无法识别。在其他情况下，它们可能会保持 MHC Ⅰ类分子的表达，并促进细胞毒性 T 淋巴细胞的免疫抑制。因此，分析肿瘤和转移灶中 MHC Ⅰ类分子的表达对于阐明这些逃逸机制非常重要。此外，有必要确定涉及这些改变的分子机制，以逆转它们并恢复肿瘤细胞上 MHC Ⅰ类分子的表达。本综述讨论了 MHC Ⅰ类分子在肿瘤进展中的作用和调节。我们重点讨论了肿瘤和转移灶中存在的改变的 MHC Ⅰ类表型，以及导致 MHC-I 改变的分子机制，强调了恢复癌细胞上 MHC Ⅰ类分子表达的机制。对每个患者的肿瘤和转移灶的 HLA Ⅰ类表型进行个体化研究，将允许根据个性化医学选择最合适的免疫治疗方法。
