Assessing microenvironment immunogenicity using tumor specimen exomes: Co-detection of TcR-[alpha]/[beta] V(D)J recombinations correlates with PD-1 expression

• Published in: International journal of cancer 2017-06, Vol.140 (11), p.2568
• Main Authors: Tu, Yaping N, Tong, Wei Lue, Samy, Mohammad D, Yavorski, John M, Kim, Minjung, Blanck, George
• Format: Article
• Language: English
• Subjects: Algorithms; Antigens; Cancer; Lymphocytes; Medical research; Melanoma; T cell receptors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30675

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-[beta] 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-[alpha] VJ recombinations, consistent with the occurrence of biallelic TcR-[alpha] recombinations and possibly consistent with the fact that only one junctional recombination is required for TcR-[alpha] whereas two recombinations are required to form a TcR-[beta] gene. Nevertheless, the ratio of productive TcR-[beta] to unproductive TcR-[beta] samples, in comparison to the ratio of productive to unproductive TcR-[alpha] or TcR-[gamma] positive-samples, is very high. This result indicates that detection of a productive TcR-[beta] 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-[alpha] and -[beta] recombinations (e.g., p