Characteristics and prognostic significance of profiling the peripheral blood T‐cell receptor repertoire in patients with advanced lung cancer

Abstract

Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor‐reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T‐cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high‐throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre‐ and post‐treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.

Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer

“…In this study, we analyzed four metrics of the TCR repertoire: diversity, clonality, MH overlap, and Vβ and Jβ gene fragment types. The stability of these factors has been previously reported . The TCR repertoire was not significantly different between the groups at baseline (Fig 2b).…”

“…Genomic DNA was extracted from peripheral blood cells by using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Multiplex PCR amplification of CDR3 of the TCR β chain was performed using the deep resolution Immunoseq platform (Geneplus‐Beijing, Beijing, China) . Reads from raw data with low quality and high N ratios were removed to obtain clean reads.…”

“…Multiplex PCR amplification of CDR3 of the TCR β chain was performed using the deep resolution Immunoseq platform (Geneplus-Beijing, Beijing, China). 18 Reads from raw data with low quality and high N ratios were removed to obtain clean reads. Two-terminal reads were merged, and the reads were subjected to bioinformatics analysis.…”

“…TCR diversity is predominantly derived from the highly variable complementarity‐determining region 3 (CDR3) and is generated by random rearrangement and junction region mutation of the V‐D‐J regions, which are three fragments located in TCR‐coding genes. Many studies have shown that lymphocytes recognize the patient's unique mutations in the peripheral blood; TCR repertoire in peripheral blood could be a biomarker of clinical outcomes for chemotherapy and immunotherapy . We predicted that the peripheral blood TCR repertoire and lymphocyte subsets reflect the immune status of patients with SCLC, and its dynamic changes can reflect immune status changes.…”

“…Many studies have shown that lymphocytes recognize the patient's unique mutations in the peripheral blood 15,16 ; TCR repertoire in peripheral blood could be a biomarker of clinical outcomes for chemotherapy and immunotherapy. [17][18][19] We predicted that the peripheral blood TCR repertoire and lymphocyte subsets reflect the immune status of patients with SCLC, and its dynamic changes can reflect immune status changes.…”