医学
结直肠癌
免疫疗法
癌症
细胞毒性T细胞
癌症研究
肿瘤科
免疫系统
化疗
内科学
癌症免疫疗法
免疫学
肿瘤微环境
CD8型
作者
Venkatesh Rajamanickam,Carmen Ballesteros-Merino,Kimberly Samson,David Ross,Brady Bernard,Bernard A. Fox,Eric Tran,Pippa Newell,Thomas Duhen
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2021-04-05
卷期号:9 (6): 602-611
标识
DOI:10.1158/2326-6066.cir-20-1024
摘要
Microsatellite-stable (MSS) colorectal cancers are characterized by low mutation burden and limited immune-cell infiltration and thereby respond poorly to immunotherapy. Here, we report a case of metastatic MSS colorectal cancer with a robust anticancer immune response. The primary tumor was resected in 2012, and the patient received several cycles of chemotherapy until 2017. In 2018, the patient underwent a left hepatectomy to remove a new metastasis. Analysis of the metastatic tumor revealed a strong CD8+ T-cell response. A high frequency of CD8+ T cells coexpressed CD39 and CD103, a phenotype characteristic of tumor-reactive cells. Using whole-exome sequencing, we identified somatic mutations that generated peptides recognized by CD39+CD103+CD8+ T cells. The observed reactivity against the tumor was dominated by the response to a single mutation that emerged in the metastasis. Somatic mutations that were not immunogenic in the primary tumor led to robust CD8+ T-cell expansion later during disease progression. Our data suggest that the cytotoxic treatment regimen received by the patient might be responsible for this effect. Hence, the capacity of cytotoxic regimens to prime the immune system in colorectal cancer patients should be investigated further and might provide a rationale for combination with immunotherapy.
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