科研之友
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摘要
T-cell receptor (TcR) recombinations can be recovered from tumor specimen, whole exome sequences (WXS) files. However, it is not yet clear how these recombinations represent lymphocytes or an anti-tumor immune response. Here we report the identification of productive TcR- recombinations in WXS files representing primary and metastatic melanoma. The recombinations are identifiable in about 20% of the cancer genome atlas melanoma samples. This frequency of detection is lower than the frequency of TcR- VJ recombinations, consistent with the occurrence of biallelic TcR- recombinations and possibly consistent with the fact that only one junctional recombination is required for TcR- whereas two recombinations are required to form a TcR- gene. Nevertheless, the ratio of productive TcR- to unproductive TcR- samples, in comparison to the ratio of productive to unproductive TcR- or TcR- positive-samples, is very high. This result indicates that detection of a productive TcR- VDJ recombination represents a comparatively high standard for potential antigen binding capacity, when employing a tumor specimen exome file for the assessment. Additionally, PD-1 expression and antigen presentation functions correlated with the co-detection of TcR- and - recombinations (e.g., p<0.0004), suggesting that co-detection of TcR- and - recombinations represents an anti-melanoma response that has been blunted by the advent of PD-1 expression. We further show that the algorithm for detecting the TcR- VDJ recombinations is applicable to exome files generated from mouse tissue, thus providing for opportunities to develop empirical paradigms for interpreting the identification of TcR V(D)J recombinations in tissue resident lymphocytes. What's new? T-cell receptor (TcR) recombinations have been identified in tumor lymphocytes. However, it has not been clear how these recombinations relate to the anti-tumor immune response. In this study, the authors developed an algorithm to analyze TcR recombinations using standard tumor exome (WXS) files. Further analysis found unusual types of TcR recombination in the files, and also revealed that the anti-tumor response in melanoma may be blunted by expression of the immune-checkpoint protein PD-1. This algorithm may allow an enhanced understanding of lymphocytes that impact tumor development, in both humans and mice.
- 出版日期2017-6-1
