Lou, Emil, Xiu, Joanne, Baca, Yasmine, Saeed, Anwaar, Prakash, Ajay, Gholami, Sepideh, Subramanian, Subbaya, Starr, Timothy K, Fontana, Elisa, Pandey, Ritu, Lenz, Heinz-Josef, Shields, Anthony F, Nabhan, Chadi, Oberley, Matthew, Seeber, Andreas, El-Deiry, Wafik (March 2024) Differential landscape of immune evasion in oncogenic RAS-driven primary and metastatic colorectal cancers. Mol Ther Oncol, 32 (1). p. 200786. ISSN 2950-3299
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Abstract
Oncogenic drivers such as KRAS extensively modulate the tumor inflammatory microenvironment (TIME) of colorectal cancer (CRC). The influence of KRAS on modulating immune cell composition remains unclear. The objective of this study was to identify signatures of infiltrative immune cells and distinctive patterns that differ between RAS wild-type (WT) and oncogenic mutant (MT) CRC that explain immune evasion in MT tumors. A total of 7,801 CRC specimens were analyzed using next-generation DNA sequencing, whole-exome sequencing, and/or whole transcriptome sequencing. Deficiency of mismatch repair (dMMR)/microsatellite instability (MSI) and tumor mutation burden (TMB) were also assessed. KRAS mutations were present in 48% of CRC, similarly distributed in patients younger than vs. 50 years and older. In microsatellite stable (MSS) KRAS MT tumors, composition of the TIME included higher neutrophil infiltration and lower infiltration of B cells. MSI-H/dMMR was significantly more prevalent in RAS WT (9.1%) than in KRAS MT (2.9%) CRC. In MSS CRC, TMB-high cases were significantly higher in RAS MT (3.1%) than in RAS WT (2.1%) tumors. KRAS and NRAS mutations are associated with increased neutrophil infiltration, with codon-specific differences. These results demonstrate significant differences in the TIME of RAS mutant CRC that match previous reports of immunoevasive characteristics of such tumors.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Gholami Lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 21 March 2024 |
| Date Deposited: | 12 Apr 2024 20:08 |
| Last Modified: | 12 Apr 2024 20:08 |
| PMCID: | PMC10963927 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41512 |
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