Characteristics of T-cell receptor repertoire between lung cancer patients and healthy people.

Abstract

e20728 Background: Deep sequencing studies on T cell receptor (TCR) repertoire have provided a wealth of information, such as immune status, virus infection history and so on. As we all known, the thymus begins to involute at the time of birth, so does the immune system. We can use TCR sequence to describe changes in human’s immune system with age, the difference between males and females and immune stat of cancers. Methods: We analyzed TCRβrepertoire in 334 healthy individuals without cancer, aged 2–83 years, and 207 lung cancers. In detail, genomic DNA was extracted from peripheral blood and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of individual T cell clones. Shannon’s entropy was calculated on the clonal abundance of all productive TCR sequences. The normalized Shannon’s entropy (Shannon index) was determined by dividing Shannon’s entropy by the natural logarithm of the number of unique productive TCR sequences. HEC was defined by a CDR3 aa clonotype clonal frequency exceeding 0.1%. Results: Analysis had been made to test the age relationship among a cluster of commonly used immune parameters, such as Shannon’s entropy, clonality and so on. Two outcomes, Shannon index and HEC, had showed a more closed correlation with age. Shannon indexs were significantly decreasing with age (p = 6.2×10-11), while HECs increased with age (p = 5.3×10-10) . Comparison of the peripheral blood T cell repertoire diversity between male and female, we found TCRβdiversity decreases more rapidly in 20 to 40 years for males than for females. No gender difference was observed in the youngest cohort and the oldest age cohort. Lung cancer patients has a lower T cell diversity compared with health people aged 40 years or more (6.43±1.30 vs 6.71±1.70, p = 6.3×10-5). Conclusions: Our data suggest that the human peripheral blood TCR repertoire diversity decrease from young ( < 20 years) to middle-aged ( 20 to 65 years ) to elderly adults ( > 65 years). Moreover, TCR repertoire displays significant gender difference in the 20-40 years age group. Lung cancer patients suffer a poorer immune state than healthy people.