美国弗雷德-哈钦森癌症中心Cyrus M. Ghajar和Stanley R. Riddell研究组合作取得一项新突破。他们的研究认为潜伏期扩散性肿瘤细胞的免疫逃逸是由于其稀缺性造成的，T细胞免疫疗法可以克服这一问题。相关论文于2024年1月8日发表在《癌细胞》杂志上。

研究人员发现，复发的源头——扩散性肿瘤细胞（DTCs）会逃避针对肿瘤新抗原的内源性免疫。虽然DTC下调了主要组织相容性复合体I，但这并不妨碍传统T细胞的识别。相反，DTC与内源性抗原特异性T细胞这两个相对稀少群体之间很少发生相互作用，这是DTC持久存在的原因。

现有三种增加肿瘤特异性T细胞数量的免疫疗法中的任何一种都能克服这种稀缺性。这三种免疫疗法分别是基于T细胞的疫苗接种，或T细胞受体或嵌合抗原受体T细胞的过继转移。每种方法都能强有力地消除DTC，有助于人们发现MHC限制性和非限制性DTC抗原，这些抗原可作为基于T细胞免疫疗法的靶点，以消除患者体内的转移启动细胞库。

据了解，从"成功"治愈局部乳腺癌到其发生远处转移之间可能存在多年间隔，这是一个尚未开发的根除扩散性疾病和预防转移的窗口期。

附：英文原文

Title: Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies

Author: Erica T. Goddard, Miles H. Linde, Shivani Srivastava, Grant Klug, Tamer B. Shabaneh, Santino Iannone, Candice A. Grzelak, Sydney Marsh, Alessandra I. Riggio, Ryann E. Shor, Ian L. Linde, Marissa Guerrero, Joshua R. Veatch, Annelise G. Snyder, Alana L. Welm, Stanley R. Riddell, Cyrus M. Ghajar

Issue&Volume: 2024/01/08

Abstract: The period between “successful” treatment of localized breast cancer and the onsetof distant metastasis can last many years, representing an unexploited window to eradicatedisseminated disease and prevent metastases. We find that the source of recurrence—disseminatedtumor cells (DTCs) —evade endogenous immunity directed against tumor neoantigens.Although DTCs downregulate major histocompatibility complex I, this does not precluderecognition by conventional T cells. Instead, the scarcity of interactions betweentwo relatively rare populations—DTCs and endogenous antigen-specific T cells—underliesDTC persistence. This scarcity is overcome by any one of three immunotherapies thatincrease the number of tumor-specific T cells: T cell-based vaccination, or adoptivetransfer of T cell receptor or chimeric antigen receptor T cells. Each approach achievesrobust DTC elimination, motivating discovery of MHC-restricted and -unrestricted DTCantigens that can be targeted with T cell-based immunotherapies to eliminate the reservoirof metastasis-initiating cells in patients.

DOI: 10.1016/j.ccell.2023.12.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00439-7