|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Kamran, SC, Lennerz, JK, Margolis, CA, Liu, D, Reardon, B, Wankowicz, SA, Van Seventer, EE, Tracy, A, Wo, JY, Carter, SL, Willers, H, Corcoran, RB, Hong, TS, Van Allen, EM|
|Journal||Clin Cancer Res|
|Date Published||2019 Jun 28|
PURPOSE: Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiation therapy (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 [R], 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 / 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. Absent 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.
|Alternate Journal||Clin. Cancer Res.|
|Grant List||U01 CA233100 / CA / NCI NIH HHS / United States|