Comprehensive T-cell receptor repertoire of Chinese lung cancer patients related with age.

Abstract

e21076 Background: Cancer is most commonly diagnosed disease worldwide and also a leading cause of death. Cancer is more common in older people, but it can also be found in younger people. As the importance of T cell receptor (TCR) repertoire gains appreciation, particularly given their potential utility for cancer immunotherapeutic prognostication, the characteristics of TCR repertoire are needed. We detected the complementarity determining region 3 (CDR3) by TCR sequence to describe the correlation between diversity and clonality in human’s immune system and age. Methods: The TCRβ repertoire of 47 stage Ia lung cancer patients were analyzed. Genomic DNA was extracted from peripheral blood or tissue, and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of patients T cell clones. Shannon index was calculated on the clonal abundance of all productive TCR sequences. Simpson index also was calculated to measure the clonality of TCR repertoire. MOI was a measure of the similarity in the T cell repertoire between tissue and blood taking into account the specific rearrangements and their respective frequencies. Results: In tissue, the Simpson index ranged from 0.00075 to 0.11466 (mean = 0.01343); Shannon index ranged from 2.91 to 8.95 (mean = 6.26). The age ranged from 27 to 78 (median = 63). Patients were divided into two groups based on median age. The older showed higher Shannon index (p = 0.005) but lower Simpson index (p = 0.0072) than younger patients in tissue. Further, the higher Shannon index was found in younger group in blood(p = 0.0411). Interestingly, the MOI of the older group was significantly higher than that of the younger group (p = 0.0181), suggesting that the older group had a relatively better TME immune response. Then, the usage of V and J gene segments were analyzed. Through statistical analysis and the frequencies of V and J gene usage, we identified that more V and J gene usage were different in older and younger patients. The TRBJ1-1 and TRBJ1-2 were more common in younger patients and TRBJ2-1 and TRBJ2-2 were more common in older patients. There was also more V gene usage different in both groups. Conclusions: Given that the use of certain TRBV regions is predominant in tumor tissues, our results suggested that there may be differences in immune responses of TME to tumors in younger and older patients.