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

Immunotherapy has produced encouraging results for many cancers, but resistance remains a significant problem necessitating strategies to identify patients who would benefit from immunotherapy alone or those who could benefit from addition of more aggressive treatments such as combinations with radiotherapy. We employ single-cell transcriptomics and spatial proteomics to track immunophenotypes in triple negative breast cancers using patient biopsies taken before and after one cycle of pembrolizumab and after a second cycle of pembrolizumab given concurrently with tumor-directed radiation therapy.

免疫治疗（immunotherapy）在多种癌症中已展现出令人鼓舞的临床疗效，但耐药性仍是亟待攻克的重大难题，亟需开发相关筛选策略以甄别出可单独从免疫治疗中获益的患者，或是可从联合放疗等更为强效的治疗方案中获益的人群。本研究采用单细胞转录组学（single-cell transcriptomics）与空间蛋白质组学（spatial proteomics）技术，通过采集患者在接受1个周期帕博利珠单抗（pembrolizumab）治疗前后、以及接受联合肿瘤定向放射治疗（tumor-directed radiation therapy）的第2个周期帕博利珠单抗治疗后的活检样本，对三阴性乳腺癌（triple negative breast cancers）中的免疫表型（immunophenotypes）进行追踪分析。