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1.
Research (Wash D C) ; 7: 0346, 2024.
Article En | MEDLINE | ID: mdl-38559676

Metastasis is the major cause of cancer-related death, and lymph node is the most common site of metastasis in breast cancer. However, the alterations that happen in tumor-draining lymph nodes (TDLNs) to form a premetastatic microenvironment are largely unknown. Here, we first report the dynamic changes in size and immune status of TDLNs before metastasis in breast cancer. With the progression of tumor, the TDLN is first enlarged and immune-activated at early stage that contains specific antitumor immunity against metastasis. The TDLN is then contracted and immunosuppressed at late stage before finally getting metastasized. Mechanistically, B and follicular helper T (Tfh) cells parallelly expand and contract to determine the size of TDLN. The activation status and specific antitumor immunity of CD8+ T cells in the TDLN are determined by interleukin-21 (IL-21) produced by Tfh cells, thus showing parallel changes. The turn from activated enlargement to suppressed contraction is due to the spontaneous contraction of germinal centers mediated by follicular regulatory T cells. On the basis of the B-Tfh-IL-21-CD8+ T cell axis, we prove that targeting the axis could activate TDLNs to resist metastasis. Together, our findings identify the dynamic alterations and regulatory mechanisms of premetastatic TDLNs of breast cancer and provide new strategies to inhibit lymph node metastasis.

2.
Bioresour Technol ; 401: 130731, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38663637

There is limited research on physiological and degradation mechanisms of yellow mealworm, a novel organic waste converter, in processing lignocellulosic wastes. This study has selected two types of lignocellulosic wastes, distillers' grains (DG) and maize straw (MS), to feed yellow mealworms. This study investigated the effects of lignocellulosic wastes on the growth, antioxidant system, microbiome, and lipidome of yellow mealworms. The relative growth of lignocellulosic waste group was not significantly different from wheat bran. The antioxidant level was elevated in DG. MS was significantly enriched in cellulose-degrading bacteria in the gut and was accompanied by disturbances in lipid metabolism. The correlation coefficients were used to construct a network connecting diet, microbiota, and lipids. The correlation analysis indicated that two sphingolipids, hexylglyceramide and dihydroglyceramide, were strongly and positively linked with the dominating species. This study provides comprehensive information on physiological and mechanism of mealworms in process of treating lignocellulosic waste.

3.
Med ; 5(4): 291-310.e5, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38417440

BACKGROUND: Immune checkpoint blockade has shown low response rates for advanced breast cancer, and combination strategies are needed. Microwave ablation (MWA) may be a trigger of antitumor immunity. This window-of-opportunity trial (ClinicalTrials.gov: NCT04805736) was conducted to determine the safety and feasibility of preoperative camrelizumab (an anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer. METHODS: Sixty participants were randomized to preoperatively receive single-dose camrelizumab alone (n = 20), MWA alone (n = 20), or camrelizumab+MWA (n = 20). A random number table was used to allocate interventions. The primary outcome was the safety and feasibility of MWA combined with camrelizumab. FINDINGS: Camrelizumab and MWA were well tolerated alone and in combination without delays in prescheduled surgery. No treatment-related grade III/IV adverse events were observed. Different from in the single-dose camrelizumab or MWA group, participants showed stable counts of blood cells after combination therapy. After combination therapy, peripheral CD8+ T cells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8+ T cells showed higher cytotoxic activity and effector memory- and tumor-specific signatures than emergent clones after combination therapy. Enhanced interactions between clonal expansional CD8+ T cells and monocytes were observed, suggesting that monocytes contributed to the enhanced functions of clonal expansional CD8+ T cells. Major histocompatibility complex (MHC) class I-related pathways and interferon signaling pathways were activated in monocytes by combination therapy. CONCLUSIONS: Camrelizumab combined with MWA was feasible for early-stage breast cancer. Peripheral CD8+ T cells were activated after combination therapy, dependent on monocytes with activated MHC class I pathways. FUNDING: This study was supported by the Natural Science Foundation of Jiangsu Province (BK20230017).


Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/chemically induced , CD8-Positive T-Lymphocytes/metabolism , Microwaves/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects
4.
Cancer Med ; 2023 Dec 22.
Article En | MEDLINE | ID: mdl-38133211

INTRODUCTION: Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis. METHODS: We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin-eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression-free survival (PFS) were analyzed by survival analysis. RESULTS: We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER- subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER- recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p < 0.001, respectively), whereas CD38+ cells within TLSs were associated with shorter PFS in ER+ recurrent tumors (p = 0.037). CONCLUSION: Our study proposes potential predictors for the clinical prognosis of patients with locoregional recurrent breast cancer, emphasizing the prognostic value of immune cells within TLSs, especially CD68+ cells.

5.
Front Mol Biosci ; 10: 1200335, 2023.
Article En | MEDLINE | ID: mdl-37275958

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients. Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs. Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy. Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.

6.
Bioresour Technol ; 381: 129141, 2023 Aug.
Article En | MEDLINE | ID: mdl-37169198

Effects of different nutrient ratios on the biochemical compositions of microalgae and the changes were rarely studied at the molecular level. In this study, the impacts of various nitrogen to phosphorus (N/P) ratios on growing of C. pyrenoidosa, as well as biochemical compositions and the metabolic regulation mechanism in mixed sewage, were investigated. The results suggested that 18 was optimal N/P ratio, while the dry weight (1.0 g/L), chlorophyll-a (Chla) (3.63 mg/L), and lipid production (0.28 g/L) were all the highest comparing with other groups. In contrast, the protein production (0.37 g/L) was the least. The nature of the regulatory mechanisms inthe metabolic pathways of these biochemical compositions was revealed by proteomic results, and there were 62 different expression proteins (DEPs) taken part in fatty acid and lipid biosynthesis metabolism (FA), amino acid biosynthesis metabolism (AA), photosynthesis (PHO), carbon fixation in photosynthetic organisms (CFP), and central carbon metabolism (CCM).


Chlorella , Microalgae , Wastewater , Chlorella/metabolism , Lipids , Nitrogen/metabolism , Phosphorus/metabolism , Proteomics , Microalgae/metabolism , Biomass
7.
J Am Chem Soc ; 145(16): 9285-9291, 2023 Apr 26.
Article En | MEDLINE | ID: mdl-37040147

Organic hierarchical branch micro/nanostructures constituted by single crystals with inherent multichannel characteristics exhibit superior potential in regulating photon transmission for photonic circuits. However, organic branch micro/nanostructures with precise branch positions are extremely difficult to achieve due to the randomness of the nucleation process. Herein, by taking advantage of the dislocation stress field-impurity interaction that solute molecules deposit preferentially along the dislocation line, twinning deformation was introduced into microcrystals to induce oriented nucleation sites, and ultimately organic branch microstructures with controllable branch sites were fabricated. The growth mechanism of these controllable single crystals with an angle of 140° between trunk and branch is attributed to the low lattice mismatching ratio (η) of 4.8%. These as-prepared hierarchical branch single crystals with asymmetrical optical waveguide characteristics have been demonstrated as an optical logic gate with multiple input/out channels, which provides a route to command the nucleation sites and offers potential applications in the organic optoelectronics at the micro/nanoscale.

8.
Inorg Chem ; 62(10): 4330-4340, 2023 Mar 13.
Article En | MEDLINE | ID: mdl-36863004

The field of supramolecular metal-organic cage catalysis has grown rapidly in recent years. However, theoretical studies regarding the reaction mechanism and reactivity and selectivity controlling factors for supramolecular catalysis are still underdeveloped. Herein, we demonstrate a detailed density functional theory study on the mechanism, catalytic efficiency, and regioselectivity of the Diels-Alder reaction in bulk solution and within two [Pd6L4]12+ supramolecular cages. Our calculations are consistent with experiments. The origins of the catalytic efficiency of the bowl-shaped cage 1 have been elucidated to be the host-guest stabilization of the transition states and the favorable entropy effect. The reasons for the switch of the regioselectivity from 9,10-addition to 1,4-addition within the octahedral cage 2 were attributed to the confinement effect and the noncovalent interactions. This work would shed light on the understanding of [Pd6L4]12+ metallocage-catalyzed reactions and provide a detailed mechanistic profile otherwise difficult to obtain from experiments. The findings of this study could also aid to the improvement and development of more efficient and selective supramolecular catalysis.

9.
J Proteomics ; 276: 104840, 2023 03 30.
Article En | MEDLINE | ID: mdl-36758853

Over the years, significant technological discoveries have facilitated the improvement of meat-related research. Recent studies of complex and interactive factors contributing to variations in meat safety are increasingly focused on data-driven omics approaches such as proteomics. This review highlighted omics advances in elucidating the biochemical and biological actions on meat safety. Also, the impacts of the nutritional characteristics of meat and meat products on human health are emphasized. Future perspectives should explore multi-omics and in situ investigations to elucidate the implications in microbiological studies, including nutritional and health-related assessments. Also, creating meat safety assessment and prediction models based on biomarkers of meat safety traits will help to mitigate application constraints, thereby evaluating meat quality more accurately. This could provide a scientific basis for increasing the meat industry's profitability and producing high-quality meat and meat products for consumers. SIGNIFICANCE OF THE REVIEW: This review highlighted omics advances in elucidating underlying mechanisms of biochemical and biological factors associated with meat safety. Also, the impacts of meat proteins on human health are emphasized. Future perspectives should explore multi-omics and in situ investigations to elucidate the implications in microbiological studies, including nutritional and health-related assessments. Also, creating meat safety assessment and prediction models based on biomarkers of meat safety traits will help to mitigate application constraints, thereby evaluating meat quality more accurately. This could provide a scientific basis for increasing the meat industry's profitability and producing high-quality meat and meat products for consumers.


Biological Factors , Meat Products , Humans , Proteomics , Meat/analysis , Biomarkers
10.
Angew Chem Int Ed Engl ; 62(11): e202216878, 2023 Mar 06.
Article En | MEDLINE | ID: mdl-36651564

Here, we report the first example of Ni-catalyzed asymmetric hydrosilylation of 1,1-disubstituted allenes with high level of regioselectivities and enantioselectivities. The key to achieve this stereoselective hydrosilylation reaction was the development of the SPSiOL-derived bisphosphite ligands (SPSiPO). This protocol features broad substrate scope, excellent functional group, and heterocycle tolerance, thus provides a versatile method for the construction of enantioenriched tertiary allylsilanes in a straightforward and atom-economic manner. DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity.

11.
Meat Sci ; 198: 109110, 2023 Apr.
Article En | MEDLINE | ID: mdl-36640717

Pale, soft and exudative (PSE) meat has worse edible quality than red, firm and non-exudative (RFN) meat, but their difference in nutritional values is still unclear. In this study, the differences in digestive properties between PSE and RFN pork were explored, and the potential mechanisms were analyzed in terms of protein conformation. The PSE pork showed significantly higher digestibility and smaller particle size compared with RFN pork (P < 0.05) after gastrointestinal digestion. Mechanistically, the lower viscosity was seen in the PSE pork digestion system. The protein structure of PSE pork was disordered with weaker hydrogen bond and ionic bond before and after heating. In addition, the protein (mainly salt-soluble protein) of PSE pork was highly oxidized. The results suggested that higher level of oxidation in PSE pork leads to the destruction of the molecular forces, resulting in the impaired protein conformation and disordered protein structure. The serial changes caused the meat proteins more accessible to digestive enzymes, thus improving the digestibility. The findings provide new insights into the evaluating the quality of PSE meat.


Pork Meat , Red Meat , Animals , Swine , Meat , Muscle Proteins/chemistry , Digestion
12.
Neuropsychologia ; 172: 108274, 2022 07 29.
Article En | MEDLINE | ID: mdl-35623449

The ability to control unwanted memories is essential for emotional regulation and maintaining mental health. Previous evidence indicates that suppressing retrieval, which recruits executive control mechanisms to prevent unwanted memories entering consciousness, can cause forgetting, termed suppression-induced forgetting (SIF). Since these executive mechanisms involve multiple mental operations, we hypothesize that the efficacy of SIF may be limited by individuals' capacity limitation of cognitive control. Here, we tested this hypothesis. Participants were assigned to two groups based on the median of their cognitive control capacity (CCC, estimated by the backward masking majority function task) and performed the think/no-think task with electrophysiological signals recorded. The results showed that the SIF effect was observed only in the high CCC group but not in the low CCC group. In accordance, repeated suppression attempts also resulted in a steeper reduction in intrusive thoughts in the high CCC group. Furthermore, ERP analysis revealed a decrease in recollection-related late parietal positivity (LPP) under the no-think condition in the high CCC group. A mediation analysis revealed that the reduced intrusive memories mediated the effect of CCC on SIF. These findings suggest that suppressing retrieval could reduce traces of the unwanted memories, making them less intrusive and harder to recall. More importantly, successful SIF is constrained by the capacity of cognitive control which may be used to ensure the coordination of multiple cognitive processes during suppression.


Cognition , Mental Recall , Cognition/physiology , Executive Function , Humans , Mental Recall/physiology
13.
J Oncol ; 2022: 1608936, 2022.
Article En | MEDLINE | ID: mdl-35444700

Background: LINC00922 has been found to promote epithelial-mesenchymal transition (EMT) in a variety of tumors. But its functions in gastric cancer (GC) remain unclear. We attempt to investigate the correlation between LINC00922 and GC via bioinformatics analysis, in vitro and in vivo experiments. Methods: TCGA and GTEx databases were utilized to obtain the RNAseq and clinical data of GC, and then, identified the correlation of LINC00922 with patients' clinicopathological characteristics and prognosis. GSEA and GO/KEGG enrichment analyses were performed to explore the potential functions or signaling pathways that LINC00922 participated in GC. Infiltration levels of immune cells were employed by ssGSEA algorithm, and then Wilcoxon rank sum test was applied to analyze their correlations with LINC00922. Scratch and transwell assays were conducted to detect the invasion and migration abilities of GC cells. Western blot was performed to explore the expression level of EMT-related proteins. Furthermore, we constructed the xenograft tumor model and metastatic tumor model in nude mice to explore the effect of LINC00922 downregulating on metastasis of GC cells in vivo. Results: Compared with normal tissues, LINC00922 was highly expressed in GC tissues and positively correlated with poor prognosis. The correlation existed between LINC00922 and immune infiltration in GC. Downregulation of LINC00922 inhibited the EMT process of GC cells. In addition, both in vitro and in vivo experiments showed that LINC00922 affects the invasion and migration abilities of GC. Conclusions: LINC00922 promotes the migration, invasion, and EMT in GC and has the potential to be used as a prognostic biomarker and therapeutic target for GC.

14.
Adv Sci (Weinh) ; 9(17): e2200033, 2022 06.
Article En | MEDLINE | ID: mdl-35403824

Minimally invasive thermal therapies have been attempted in the treatment of breast cancer, and the immune response induced by these therapies has not been fully reported. A clinical trial is performed to determine the effect of microwave ablation (MWA) in the treatment of early-stage breast cancer. The authors perform single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from six patients before and after ablation. NK and CD8+ T cells are activated by MWA of breast cancer, with the increased inhibitory signature of CD8+ T cells but not dysfunctional. Enhanced co-stimulatory signature of CD4+ T cells is observed and increased frequency of ICOS+ CD4+ T cells after MWA is confirmed by flow cytometric analysis. After ablation, T-cell clones expand with increased T-cell receptor diversities. Activated antigen receptor-mediated signaling pathways are found in B cells. Enhanced interactions between B cells and CD4+ T cells are found, indicating that B cells are important antigen-presenting cells that initiate CD4+ T cells in MWA-induced immune response. Blockade of CTLA-4 or PD-1 of post-MWA PBMCs show higher T-cell activity than that of pre-MWA PBMCs. This study provide global characteristics of MWA-induced systemic immune response and pave a way for the identification of potential targets to improve the immune response.


Breast Neoplasms , Breast Neoplasms/surgery , CD8-Positive T-Lymphocytes/metabolism , Female , Humans , Immunity , Leukocytes, Mononuclear , Microwaves/therapeutic use
15.
J Immunol Methods ; 504: 113264, 2022 05.
Article En | MEDLINE | ID: mdl-35341759

The vaccine development strategies have evolved from using an entire organism as an immunogen to a single antigen and further towards an epitope. Since an epitope is a relatively tiny and immunologically relevant part of an antigen, it has the potential to stimulate more robust and specific immune responses while causing minimal adverse effects. As a result, the recent focus of vaccine development has been to develop multi-epitope vaccines that can target multiple virulence mechanisms. Accordingly, we designed multi-epitope vaccine candidates B (multi-B-cell epitope immunogen) and CTB-B (an adjuvant - cholera toxin subunit B (CTB) - attached to immunogen B) against S. aureus by employing immunoinformatics approaches. The designed vaccines are composed of B-cell epitope segments (20-mer) of the eight well-characterized S. aureus virulence factors, namely ClfB, FnbpA, Hla, IsdA, IsdB, LukE, SdrD, and SdrE connected in series. The designed vaccines were expressed, purified, and administered to C57BL/6 mice with Freund adjuvant to evaluate the immunogenicity and protective efficacy. The results revealed that the immunized mice showed high IgG titers for the immunogen, and the antibody titers increased significantly following the second immunization. However, the generated antibodies did not protect the mice from infection. The interaction of anti-B antibodies with source virulence factors showed that the generated antibodies have no binding affinity with any of the corresponding virulence factors. Our results demonstrate the limitation of the in silico designed B-cell multi-epitope vaccine and suggest that a protein domain carrying both linear and conformational B-cell epitopes might be a better choice for developing an effective multi-epitope vaccine against S. aureus.


Staphylococcal Infections , Vaccines , Animals , Antibodies , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Mice , Mice, Inbred C57BL , Staphylococcal Infections/prevention & control , Staphylococcus aureus , Virulence Factors
16.
Psychophysiology ; 59(4): e13991, 2022 04.
Article En | MEDLINE | ID: mdl-34932832

Although accumulating evidence has revealed the effect of mindfulness training on the reduction of general stress and the improvement of mental well-being, the underlying mechanism remains unclear. In this study, we investigated whether interoceptive attention to respiratory signals plays a role. Healthy adults were randomly assigned to either receive an 8-week mindfulness training (n = 29) or inactive control (n = 28). The pre- and post-training self-reported states of negative mood were assessed together with an objective measure of interoceptive attention to respiration. Compared to the control group, mindfulness training led to a decrease in the level of negative mood and an increase in interoceptive sensitivity. Mediation analysis further showed that the effect of mindfulness training on the reduction of negative mood was fully mediated by increased interoceptive sensitivity. These results suggest that mindfulness training effectively alleviates negative mood by enhancing interoceptive attention to respiratory signals.


Interoception , Mindfulness , Adult , Affect , Humans , Mindfulness/methods
17.
Phys Rev Lett ; 127(20): 209402, 2021 Nov 12.
Article En | MEDLINE | ID: mdl-34860064
18.
Nat Nanotechnol ; 16(10): 1099-1105, 2021 Oct.
Article En | MEDLINE | ID: mdl-34400821

Conventional laser cavities require discontinuity of material property or disorder to localize a light field for feedback. Recently, an emerging class of materials, twisted van der Waals materials, have been explored for applications in electronics and photonics. Here we propose and develop magic-angle lasers, where the localization is realized in periodic twisted photonic graphene superlattices. We reveal that the confinement mechanism of magic-angle lasers does not rely on a full bandgap but on the mode coupling between two twisted layers of photonic graphene lattice. Without any fine-tuning in structure parameters, a simple twist can result in nanocavities with strong field confinement and a high quality factor. Furthermore, the emissions of magic-angle lasers allow direct imaging of the wavefunctions of magic-angle states. Our work provides a robust platform to construct high-quality nanocavities for nanolasers, nano light-emitting diodes, nonlinear optics and cavity quantum electrodynamics at the nanoscale.

19.
Infect Immun ; 89(10): e0034221, 2021 09 16.
Article En | MEDLINE | ID: mdl-34227839

In the Gram-positive pathogen Staphylococcus aureus, pore-forming toxins (PFTs), such as leukocidins and hemolysins, play prominent roles in staphylococcal pathogenesis by killing host immune cells and red blood cells (RBCs). However, it remains unknown which combination of toxin antigens would induce the broadest protective immune response against those toxins. In this study, by targeting six major staphylococcal PFTs (i.e., gamma-hemolysin AB [HlgAB], gamma-hemolysin CB [HlgCB], leukocidin AB [LukAB], leukocidin ED [LukED], Panton-Valentine leukocidin [LukSF-PV], and alpha-hemolysin [Hla]), we generated 10 recombinant toxins or toxin subunits, 3 toxoids, and their rabbit antibodies. Using the cytolytic assay for RBCs and polymorphonuclear cells (PMNs), we determined the best combination of toxin antibodies conferring the broadest protection against those staphylococcal PFTs. Although anti-HlgA IgG (HlgA-IgG) showed low cross-reactivity to other toxin components, it was essential to protect rabbit and human RBCs and human PMNs. For the protection of rabbit RBCs, HlaH35L toxoid-IgG was also required, whereas for human PMNs, LukS-IgG and LukAE323AB-IgG were essential too. When the toxin/toxoid antigens HlgA, LukS-PV, HlaH35L, and LukAE323AB were used to immunize rabbits, they increased rabbit survival; however, they did not block staphylococcal abscess formation in kidneys. Based on these results, we proposed that the combination of HlgA, LukS, HlaH35L, and LukAE323AB is the optimal vaccine component to protect human RBCs and PMNs from staphylococcal PFTs. We also concluded that a successful S. aureus vaccine requires not only those toxin antigens but also other antigens that can induce immune responses blocking staphylococcal colonization.


Staphylococcal Infections/immunology , Staphylococcus aureus/immunology , Vaccines, Combined/immunology , Animals , Bacterial Proteins/immunology , Bacterial Toxins/immunology , Cross Reactions/immunology , Erythrocytes/immunology , Erythrocytes/microbiology , Exotoxins/immunology , Hemolysin Proteins/immunology , Humans , Immunization/methods , Leukocidins/immunology , Neutrophils/immunology , Neutrophils/microbiology , Rabbits , Staphylococcal Infections/microbiology , Toxoids/immunology
20.
J Immunother Cancer ; 9(4)2021 04.
Article En | MEDLINE | ID: mdl-33795388

BACKGROUND: Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported. METHODS: The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed. RESULTS: Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor. CONCLUSIONS: MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.


Ablation Techniques , Breast Neoplasms/surgery , Inducible T-Cell Co-Stimulator Protein/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Microwaves/therapeutic use , Th1 Cells/immunology , Tumor Microenvironment/immunology , Ablation Techniques/adverse effects , Adult , Aged , Aged, 80 and over , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Case-Control Studies , Female , Humans , Microwaves/adverse effects , Middle Aged , Neoplasm Staging , Phenotype , Signal Transduction , Th1 Cells/metabolism , Time Factors , Treatment Outcome
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