TO THE EDITOR:
Tran and colleagues note that thousands of patients per year in the United States could be eligible for T-cell-based immune-therapy targeting KRAS G12D. We agree. In our National Institutes of Health-funded, population-based study, we have characterized 4346 colorectal adenocarcinomas since 1998.1 To date, the prevalence of KRAS mutations is 1441 of 4346 (33.2%), with 37.9% of the KRAS-positive tumors harboring G12D mutations. HLA typing available for 3734 patients shows that 687 (18.4%) have at least one copy of HLA-C*08:02. We found that 85 of 3734 patients (2.3%) with colorectal cancer share the same HLA type and KRAS mutation as described by Tran et al. We have also sequenced the T-cell receptor (TCR) beta chain of tumor-infiltrating lymphocytes to characterize the adaptive immune response in 295 tumors so far, in addition to expert pathological assessment.2 We detected 6338 shared TCR-β sequences among 2 or more patients, including 5 TCR-β sequences uniquely shared among patients with tumors positive for KRAS G12D and HLA-C*08:02 and 7 TCR-β sequences also shared by patients with KRAS G12D and HLA-C*08:02 and other combinations of KRAS mutations and HLA (Fig. 1).
Figure 1.
Patients with Shared T-Cell Receptor β Sequences Whose Tumors Harbor KRAS Mutations Presented by HLA-C*08:02.
Footnotes
No potential conflict of interest relevant to this letter was reported.
Contributor Information
Asaf Maoz, USC Norris Comprehensive Cancer Center Los Angeles, CA
Gad Rennert, Technion Carmel Medical Center Haifa, Israel
Stephen B. Gruber, USC Norris Comprehensive Cancer Center Los Angeles, CA, sgruber@usc.edu
References
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