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Title: Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures
Authors: Teng, Yvonne HF 
Quah, Hong Sheng 
Suteja, Lisda
Dias, Joao ML
Mupo, Annalisa
Bashford-Rogers, Rachael JM
Vassiliou, George S
Chua, Melvin LK
Tan, Daniel SW 
Lim, Darren WT 
Iyer, N Gopalakrishna 
Keywords: Science & Technology
Life Sciences & Biomedicine
T cell receptor
Immune repertoire sequencing
Tumor-infiltrating T cells
Public TCR
TCR sharing
Issue Date: 27-Sep-2021
Publisher: SPRINGER
Citation: Teng, Yvonne HF, Quah, Hong Sheng, Suteja, Lisda, Dias, Joao ML, Mupo, Annalisa, Bashford-Rogers, Rachael JM, Vassiliou, George S, Chua, Melvin LK, Tan, Daniel SW, Lim, Darren WT, Iyer, N Gopalakrishna (2021-09-27). Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures. CANCER IMMUNOLOGY IMMUNOTHERAPY 71 (4) : 989-998. ScholarBank@NUS Repository.
Abstract: Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies.
ISSN: 0340-7004
DOI: 10.1007/s00262-021-03047-7
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