《科学》子刊：“ Ter细胞”可增强癌细胞耐药性

编辑翻译：菁菁

译文校对：奇奇

文献在2021年2月最新的美国医学学术期刊《科学-转化医学》（Science Translational Medicine）首次刊发，文献发现Ter细胞在癌细胞耐药、肿瘤进展中扮演重要角色。

靶向放疗通常应用于癌症的相关研究和治疗。芝加哥大学医学部的一个多学科研究团队最近研究了一种细胞，该细胞可以释放一种蛋白质。这种蛋白质起到增强癌细胞对癌症疗法耐受性、加速肿瘤进展的作用。

这项研究发表于2021年2月24日的《科学转化医学》。研究主要关注Ter细胞，它们是分泌神经肽青蒿素的髓外红系前体。研究人员表明，局部肿瘤放疗、全身免疫疗法或两种疗法相结合，能够耗尽脾脏中的Ter细胞，减少artemin的产生，并限制放疗区域内及放疗区域外的肿瘤进展。

芝加哥大学放射与细胞肿瘤学教授、丹尼尔·K·路德维希癌症研究所教授Ralph Weichselbaum博士说，研究结果锁定了几个可能“改善放射和免疫疗法后临床结果”的靶标。他认为这些方法的前景是令人兴奋的。

这项研究使用了动物模型和三组不同患者样本。这些患者接受了放疗和化疗、放射免疫疗法等组合以治疗各种癌症，如肺癌和黑色素瘤。

作者们说，Ter细胞耗竭、artemin信号传导阻滞和免疫疗法的组合增强了对小鼠肿瘤的控制。他们指出，Ter细胞的消耗依赖于干扰素-γ介导的完整适应性免疫反应。

Weichselbaum说，在研究模型中，靶向Ter artemin轴增强了免疫疗法的功效 。在接受放疗、放射免疫疗法的患者中，Ter细胞数量减少、artemin和artemin相关信号的表达降低均与临床结果改善有关。

作者团队认为：“总的来说，我们的研究证明放射疗法、免疫疗法与肿瘤诱导的脾Ter细胞之间有相互影响的调节作用。”

作者团队说：“我们还需要进一步研究这些结合了免疫疗法和放射疗法的治疗组合，以了解它们与肿瘤促进途径之间的相互作用。”

英文原文

Study uncovers inhibitory role of 'Ter cells' in cancer therapies 

Targeted radiation is often used to study and treat diverse cancer types. A multidisciplinary research team based at the University of Chicago Medicine has recently focused on a type of cell that releases a protein that enhances resistance to cancer therapies and promotes tumor progression.

The study focused on Ter cells, which are extra medullary erythroid precursers that secrete the neuropeptide artemin. In the study, published February 24, 2021, in Science Translational Medicine, the researchers showed that local tumor radiotherapy, systemic immunotherapy or the combination of both treatments were able to deplete Ter cells in the spleen, reduce artemin production and limit tumor progression both in the locally irradiated tumors as well as outside the radiation fields.

The results identified several targets that could "potentially improve outcomes after radio- and immunotherapy," said Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor and chair of radiation and cellular oncology at the University of Chicago. "The promise of these approaches is exciting."

This study used animal models and samples from three different groups of patients who had received some combination of radiotherapy and chemotherapy, immunotherapy and radio-immunotherapy respectively for various forms of cancer, including lung cancer and melanoma.

Combinations of Ter cell depletion, blockade of artemin signaling, and immunotherapy, according to the authors, led to enhanced control of tumor burden in mice. Ter cell depletion, the authors noted, was dependent on an intact adaptive immune response, mediated by interferon-y.

Targeting the Ter artemin axis "enhanced the efficacy of immunotherapy in model systems," Weichselbaum said. Reduced numbers of Ter cells and reduced expression of artemin and artemin signaling partners were all associated with improved outcomes in patients receiving radiotherapy, radioimmunotherapy and immunotherapy.

"Together, our study demonstrates the mutually apposing regulatory effects between radiotherapy or immunotherapy and tumor-induced splenic Ter cells," the authors suggest.

These immunotherapies and combined treatments with radiotherapy, according to the authors, "warrant further research to understand the interactions between them and tumor-promoting pathways."

参考文献：

More information: Y. Hou at Xi'an Jiaotong University in Xi'an, China el al., "Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity," Science Translational Medicine (2021).

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