乳腺癌免疫治疗史：从传统免疫治疗到CAR-T技术

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A Perspective of Immunotherapy for Breast Cancer: Lessons Learned and Forward Directions for All Cancers

乳腺癌免疫治疗史：从传统免疫治疗到CAR-T技术

摘要: 肿瘤免疫治疗从50年前开始就是一个焦点。在此时的治疗方式优于细胞活性因子的克隆，此时对调节性T细胞所致甚少，几乎不知道间充质干细胞（原成纤维细胞克隆形成单位[落）可以通过炎症微环境来抑制免疫反应。鉴于当时的信息，从外周血抽取的单核细胞在体外活化，然后输入癌症患者体内进行治疗。目的是利用这些活化的免疫细胞来靶向对抗癌细胞。这些研究不会有长期的有效性，因为注入病人体内活化的细胞主要是原位间充质干细胞，它能够向肿瘤部位移动，然后对免疫细胞发挥抑制作用。由MSCs引起的免疫抑制也会使得调节性T细胞扩增，从而导致对肿瘤的保护。随着时间的推移，这些不同领域的治疗方法融合到一个新的方法，即用免疫手段治疗癌症。本文讨论了这些方法，并对使用CAR-T在未来治疗一些实体肿瘤如乳腺癌做了一些评论。

关键词：CAR-T细胞，间充质干细胞，T细胞，肿瘤干细胞

ABSTRACT: Immunotherapy for cancer has been a focus 50 years ago. At the time, this treatment was developed prior to cloning of the cytokines, no knowledge of regulatory T-cells, and very little information that mesenchymal stem cells (MSCs) (originally colony forming unit-fibroblasts [CFU-F]) could be licensed by the inflammatory microenvironment to suppress an immune response. Given the information available at that time, mononuclear cells from the peripheral blood were activated ex vivo and then replaced in the patients with tumor. The intent was to harness these activated immune cells to target the cancer cells. These studies did not lead to long-term responses because the activated cells when reinfused into the patients were an advantage to the resident MSCs, which can home the tumor and then become suppressive in the presence of the immune cells. The immune suppression caused by MSCs would also expand reg-ulatory T-cells, resulting instead in tumor protection. As time progressed, these different fields converged into a new approach to use immunotherapy for cancer. This article discusses these approaches and also reviews chimeric antigen receptor in the context of future treatments for solid tumors, including breast cancer.

KEYWORDS: CAR T-cell, mesenchymal stem cell, T-cells, cancer stem cells

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