美国雪松-西奈医疗中心Simon R.V. Knott、Stephen L. Shiao及德克萨斯西南医学中心Heather McArthur课题组合作的最新研究，利用单细胞和空间图谱分析确定了三阴性乳腺癌患者对pembrolizumab和放疗三种响应的机制。这一研究成果发表在2024年1月8日出版的国际学术期刊《癌细胞》上。

研究人员采用单细胞转录组学和空间蛋白质组学对三阴性乳腺癌活检组织进行了分析，这些活检组织分别取自基线、使用一个周期的Pembrolizumab后以及在第二周期使用Pembrolizumab与放疗联合治疗。无应答者在治疗前后缺乏免疫浸润，治疗引起的免疫变化极小。

有反应的肿瘤在治疗前可通过分类器分为两组，一组在治疗前表现为主要组织相容性复合体高表达，有三级淋巴结构特征，并显示出抗肿瘤免疫。另一组反应者基线类似于非反应者，只有在联合治疗后才会产生最大的免疫反应，其特点是细胞毒性T细胞和抗原呈递骨髓细胞相互作用，这在三阴性乳腺癌的小鼠模型中得到了验证。

据悉，需要制定策略以更好地确定哪些患者可从单纯的免疫疗法中获益，哪些患者可能需要化疗或放疗等其他疗法来克服耐药性。

附：英文原文

Title: Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer

Author: Stephen L. Shiao, Kenneth H. Gouin, Nathan Ing, Alice Ho, Reva Basho, Aagam Shah, Richard H. Mebane, David Zitser, Andrew Martinez, Natalie-Ya Mevises, Bassem Ben-Cheikh, Regina Henson, Monica Mita, Philomena McAndrew, Scott Karlan, Armando Giuliano, Alice Chung, Farin Amersi, Catherine Dang, Heather Richardson, Wonwoo Shon, Farnaz Dadmanesh, Michele Burnison, Amin Mirhadi, Zachary S. Zumsteg, Rachel Choi, Madison Davis, Joseph Lee, Dustin Rollins, Cynthia Martin, Negin H. Khameneh, Heather McArthur, Simon R.V. Knott

Issue&Volume: 2024/01/08

Abstract: Strategies are needed to better identify patients that will benefit from immunotherapyalone or who may require additional therapies like chemotherapy or radiotherapy toovercome resistance. Here we employ single-cell transcriptomics and spatial proteomicsto profile triple negative breast cancer biopsies taken at baseline, after one cycleof pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy.Non-responders lack immune infiltrate before and after therapy and exhibit minimaltherapy-induced immune changes. Responding tumors form two groups that are distinguishableby a classifier prior to therapy, with one showing high major histocompatibility complexexpression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunitybefore treatment. The other responder group resembles non-responders at baseline andmounts a maximal immune response, characterized by cytotoxic T cell and antigen presentingmyeloid cell interactions, only after combination therapy, which is mirrored in amurine model of triple negative breast cancer.

DOI: 10.1016/j.ccell.2023.12.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00440-3