Longitudinal change trend of the TCR repertoire reveals the immune response intensity of the inactivated COVID-19 vaccine.

Evidence concerning the individual differences in neutralizing antibody responses after receiving the COVID-19 vaccine remains lacking. In this study, we collected the serum and Peripheral blood mononuclear cells(PBMC) of 16 subjects who had never suffered from COVID-19 before during the course of two vaccine doses. Microneutralization assay is used to determine the immune response intensity of vaccine subjects. we revealed the change trend of TCR diversity using T cell receptor (TCR) sequencing. Then, we analyzed the correlation between HLA class II allele frequencies and the intensity of immune response. Finally, we identified several CDR3 sequences related to the intensity of the immune response. We analyzed the differences in D50 (DD50) between different time points, and found that there were two patterns in the change trend of TCR diversity, and the increased diversity group has stronger immune response. The inactivated vaccine is different from the mRNA vaccine against the spike protein, resulting in differences in TCR repertoire response patterns and antibody responses, which are related to HLA-DRB1 * 09:01. The presence of specific CDR3 sequences in the increased diversity group, rather than gene usage of the VJ gene, determines the intensity and persistence of neutralizing antibody titers. Finally, We identified the different response patterns of the human TCR repertoire to inactivated vaccines. The pattern with increased diversity is more likely to appear strong and more lasting immune response.

The biomarkers related to immune infiltration to predict distant metastasis in breast cancer patients.

Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis. Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism. Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful. Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.