癌*史：從傳統(tǒng)*到CAR-T技術(shù)
A Perspective of Immunotherapy for Breast Cancer: Lessons Learned and Forward Directions for All Cancers
癌*史：從傳統(tǒng)*到CAR-T技術(shù)
摘要: 腫瘤*從50年前開始就是一個焦點。在此時的治療方式優(yōu)于細胞活性因子的克隆，此時對調(diào)節(jié)性T細胞所致甚少，幾乎不知道間充質(zhì)干細胞（原成纖維細胞克隆形成單位[落）可以通過炎癥微環(huán)境來抑制免疫反應(yīng)。鑒于當時的信息，從外周血抽取的單核細胞在體外活化，然后輸入癌癥患者體內(nèi)進行治療。目的是利用這些活化的免疫細胞來靶向?qū)拱┘毎?。這些研究不會有*的有效性，因為注入病人體內(nèi)活化的細胞主要是原位間充質(zhì)干細胞，它能夠向腫瘤部位移動，然后對免疫細胞發(fā)揮抑制作用。由MSCs引起的免疫抑制也會使得調(diào)節(jié)性T細胞擴增，從而導(dǎo)致對腫瘤的保護。隨著時間的推移，這些不同領(lǐng)域的治療方法融合到一個新的方法，即用免疫手段治療癌癥。本文討論了這些方法，并對使用CAR-T在未來治療一些實體腫瘤如癌做了一些評論。
關(guān)鍵詞：CAR-T細胞，間充質(zhì)干細胞，T細胞，腫瘤干細胞
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
