Circulating T-Cell Repertoires Correlate With the Tumor Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NAC) has been widely used in patients with breast cancer to minish tumor burden and increase resection rate of cancer. T-cell repertoire has been believed to be able to monitor antitumor immune responses. This study aimed to explore the dynamic change of T-cell repertoire and its clinical value in evaluating the tumor response in patients with breast cancer receiving NAC. MATERIALS AND METHODS: Ninety-four patients who underwent NAC before surgery were recruited, and peripheral blood samples were collected at multiple time points during NAC. High-throughput T-cell receptor (TCR)-ß sequencing was used to characterize the T-cell repertoire of every sample and analyzed the changes in circulating T-cell repertoire during NAC. RESULTS: We found that the diversity of TCR repertoires was associated with age and clinical stage of the patients with breast cancer. The distribution of Vß and Jß genes in TCR repertoires was skewed in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Vß20.1 and Vß30 expression levels before NAC correlate with tumor response after all cycles of NAC in HER2- and HER2+ patients, respectively. Some CDR3 motifs that correlated with clinical response in either HER2+ or HER2- patients were identified. Besides, TCR repertoire evolved during NAC and the diversity of TCR repertoire decreased more after two cycles of NAC in patients with good tumor response after all cycles of NAC (P = .0061). CONCLUSION: Our results demonstrated that TCR repertoire correlated with the characteristics of the tumor, such as the expression status of HER2. Moreover, some characteristics of TCR repertoires that correlated with clinical response were identified and they might provide useful information to tailor therapeutic regimens at the early cycle of NAC.

The Diagnostic and Prognostic Potential of the B-Cell Repertoire in Membranous Nephropathy.

Membranous nephropathy (MN), an autoimmune glomerular disease, is one of the most common causes of nephrotic syndrome in adults. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A new method for diagnosis and prognosis surveillance is urgently needed for patients. In the present study, we recruited 66 MN patients before any treatment and 11 healthy control (HC) and analyzed multiple aspects of the immunoglobulin heavy chain (IGH) repertoire of these samples using high-throughput sequencing. We found that the abnormalities of CDR-H3 length, hydrophobicity, somatic hypermutation (SHM), and germ line index were progressively more prominent in patients with MN, and the frequency of IGHV3-66 in post-therapy patients was significantly lower than that in pre-therapy patients. Moreover, we found that the IGHV3-38 gene was significantly related to PLA2R, which is the most commonly used biomarker. The most important discovery was that several IGHV, IGHD transcripts, CDR-H3 length, and SHM rate in pre-therapy patients had the potential to predict the therapeutic effect. Our study further demonstrated that the IGH repertoire could be a potential biomarker for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires sheds new light on the detection and surveillance of MN.

The Landscape and Prognosis Potential of the T-Cell Repertoire in Membranous Nephropathy.

Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease. It is widely accepted now that MN is an immune-related disease that involves the whole immune system. In this study, we analyzed the T-cell receptor beta chain (TCRß) repertoire of the circulating T lymphocytes of MN patients and healthy controls using high-throughput sequencing. We compared multiple aspects of the TCRß repertoire, including diversity and the Vß and Jß genes between MN patients and healthy controls, and we found that the diversities within the VJ cassette combination in the peripheral blood of MN patients were lower than in the healthy controls. We also found the TCRß repertoire similarity between pre- and post-therapy could reflect the clinical outcome, and two Vß genes in pre-therapy had the potential to predict the therapeutic effect. These findings indicated the potential of the TCRß repertoire as non-invasive biomarkers for the prognosis prediction of MN. The characteristics of circulating T-lymphocyte repertoires shed light on MN detection, treatment, and surveillance.