Notes

Expression along with Value of WNT4 in Ectopic along with Eutopic Endometrium regarding Human being Endometriosis.
T-cell responses were analyzed against a panel of AKF9 variants with single amino-acid substitutions, in which mutations did not alter the high HLA-binding affinity and stability. The responses varied across individuals, demonstrating the impact of heterogeneous T-cell repertoires in this human cancer model. Moreover, responses were biased toward a variant group with large structural changes compared to the wild-type peptide. Thus, naive T-cell induction can be attributed to multiple determinants. Combining structural dissimilarity with gene-expression levels, HLA-binding affinity, and stability may further help prioritize the immunogenicity of non-anchor-type neoantigens.Genetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the "NP" rule. 4-PBA in vitro By integrating this rule with an existing prediction algorithm, we found improved performance in neoantigen prioritization. To better understand this rule, we solved several neoantigen/MHC structures. These structures showed that neoantigens that follow this rule not only increase peptide-MHC binding affinity but also create new TCR-binding features. These molecular insights highlight the value of immune-based classification in neoantigen studies and may enable the design of more effective cancer immunotherapies.Recent advances in immunotherapy, as a part of the multidisciplinary therapy, has gradually gained more attention. However, only a small proportion of patients who sensitive to the therapy could gain benefits. An increasing number of studies indicate that intestinal microbiota could enhance the efficiency of cancer immunotherapy. As one of the main probiotics, Bifidobacterium plays an important role in immune regulation, which has been proved by animal research and human clinical study. But the detailed mechanism was not clearly elucidated. Here we found oral administration of Bifidobacterium breve (B. breve) lw01 could significantly inhibit tumor growth and up-regulate tumor cell apoptosis, which relied on the recruitment of tumor-infiltrating lymphocytes and dendritic cells (DCs) in tumor microenvironment, but not Lactobacillus rhamnosus (L. rhamnosus) CGMCC 1.3724 or Escherichia coli (E. coli) MG1655. In the in situ ligated intestine loop model, B. breve's stimulation triggered the upregulated expression of DC-related chemokine CCL20 and recruited more DCs in the intestinal villi. Further study revealed the enhancement of interleukin 12 (IL-12) secretion derived from DCs is essential to B. breve's antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous B. breve might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via B. breve.Somatic mutations of STK11 or KEAP1 are associated with poor clinical outcomes for advanced non-small-cell lung cancer (aNSCLC) patients receiving immune checkpoint inhibitors (ICIs), chemotherapy, or targeted therapy. Which treatment regimens work better for STK11 or KEAP1 mutated (SKmut) aNSCLC patients is unknown. In this study, the efficacy of atezolizumab versus docetaxel in SKmut aNSCLC was compared. A total of 157 SKmut aNSCLC patients were identified from POPLAR and OAK trials, who were tested by blood-based FoundationOne next-generation sequencing assay. Detailed clinical data and genetic alterations were collected. Two independent cohorts were used for biomarker validation (n = 30 and 20, respectively). Median overall survival was 7.3 months (95% confidence interval [CI], 4.8 to 9.9) in the atezolizumab group versus 5.8 months (95% CI, 4.4 to 7.2) in the docetaxel group (adjusted hazard ratio [HR] for death, 0.70; 95% CI, 0.49 to 0.99; P = .042). Among atezolizumab-treated patients, objective response rate, disease control rate, and durable clinical benefit were higher when blood tumor mutation burden (bTMB) and PD-L1 being higher (biomarker 1, n = 61) or with FAT3 mutation-positive tumors (biomarker 2, n = 83) than otherwise. The interactions for survival between these two biomarkers and treatments were significant, which were further validated in two independent cohorts. In SKmut patients with aNSCLC, atezolizumab was associated with significantly longer overall survival in comparison to docetaxel. Having FAT3 mutation or high TMB and PD-L1 expression potentially predict favorable response in SKmut patients receiving atezolizumab.Immune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. In this study, we collected tumor tissues and peripheral blood samples from 25 patients with advanced kidney cancer before anti-programmed cell death protein 1 (PD-1) treatment and 1, 3, and 6 months after treatment initiation. Furthermore, we applied a next-generation sequencing approach to characterize T cell receptor (TCR) alpha and beta repertoires. TCR repertoire analysis revealed that the responders to anti-PD-1 showed an expansion of certain T cell clones even in the blood, as evidenced by the significant decrease in the TCR diversity index and increase in the number of expanded TCR clonotypes 1 month after treatment. Interestingly, these expanded TCR clonotypes in the peripheral blood were significantly shared with tumor-infiltrating T cells in responders, indicating that they have many circulating T cells that may recognize cancer antigens. Expression analysis also revealed that 1 month after treatment, T cells from the peripheral blood of responders showed significantly elevated transcriptional levels of Granzyme B, Perforin, CD39, and PD-1, markers of cancer-associated antigen-specific T cells. Altogether, we propose that global TCR repertoire analysis may allow identifying early surrogate biomarkers in the peripheral blood for predicting clinical responses to anti-PD-1 monotherapy.
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