期刊
CLINICAL CANCER RESEARCH
卷 25, 期 18, 页码 5561-5571出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-0908
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资金
- Damon Runyon Foundation
- NCI [R01CA227388, K08 CA188615, R37 CA222574, U01 CA233100, U01CA220714]
- NIH [R01 CA225655]
Purpose: Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized. Experimental Design: We performed integrated whole-exome/transcriptome sequencing and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at time of resection (post-CRT) in 17 patients [8 complete/partial responders, 9 nonresponders (NR)]. Results: CRT was not associated with increased tumor mutational burden or neoantigen load and did not alter the distribution of established somatic tumor mutations in rectal cancer. Concurrent KRAS/TP53 mutations (KP) associated with NR tumors and were enriched for an epithelial-mesenchymal transition transcriptional program. Furthermore, NR was associated with reduced CD4/CD8 T-cell infiltrates and a post-CRT M2 macrophage phenotype. Absence of any local tumor recurrences, KP/NR status predicted worse progression-free survival, suggesting that local immune escape during or after CRT with specific genomic features contributes to distant progression. Conclusions: Overall, while CRT did not impact genomic profiles, CRT impacted the tumor immune microenvironment, particularly in resistant cases.
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