Assessing microenvironment immunogenicity using tumor specimen exomes: Co‐detection of TcR‐α/β V(D)J recombinations correlates with PD‐1 expression

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‐β recombinations in WXS file...

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Veröffentlicht in:International journal of cancer 2017-06, Vol.140 (11), p.2568-2576
Hauptverfasser: Tu, Yaping N., Tong, Wei Lue, Samy, Mohammad D., Yavorski, John M., Kim, Minjung, Blanck, George
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Sprache:eng
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Zusammenfassung: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‐β 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‐α VJ recombinations, consistent with the occurrence of biallelic TcR‐α recombinations and possibly consistent with the fact that only one junctional recombination is required for TcR‐α whereas two recombinations are required to form a TcR‐β gene. Nevertheless, the ratio of productive TcR‐β to unproductive TcR‐β samples, in comparison to the ratio of productive to unproductive TcR‐α or TcR‐γ positive‐samples, is very high. This result indicates that detection of a productive TcR‐β 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‐α and ‐β recombinations (e.g., p 
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.30675