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  • ||||||||||  [VIRTUAL] Innate-like Chemokine Receptor Profile and Migratory Behaviour By Terminally Differentiated and Educated NK Cells (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_1789;    
    Interestingly, receptors which expression declines during NK cell differentiation (CCR5, CCR7, and CXCR3) are commonly associated with adaptive T cell responses to viruses, whereas receptors that are upregulated along the differentiation axis (CXCR1, CXCR2, CX3CR1, CMKLR1) are typical for neutrophils and macrophages as a part of the innate immune response. Thus, our results suggest that NK cell differentiation and education processes together shape the NK cell migratory capabilities to promote homing of the most functional NK cell subsets to the site of inflammation and serve as the first line of defense in the immune response to pathogens and tumors.
  • ||||||||||  [VIRTUAL] Integrated Cytof, Scrna-Seq and Cite-Seq Analysis of Bone Marrow Immune Microenvironment in the Mmrf Commpass Study (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_1113;    
    P=N/A
    Our preliminary results suggested good concordance of immune cell type abundance identified in CyTOF, scRNA-seq and CITE-seq as well as concordant expression of some canonical cell type markers between RNA level and protein level. This work provides the field with reference data sets and shows more detailed examination of NK and T cell subsets is needed when handling single cell sequencing with different modalities.
  • ||||||||||  Blincyto (blinatumomab) / Astellas, Amgen
    [VIRTUAL] Obesity Attenuates T-Cell Function Which Impacts the Efficacy of T-Cell Based Immunotherapies in Acute Lymphoblastic Leukemia (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_782;    
    In contrast, we found that ACM significantly compromised the efficacy Blinatumomab with only 30% of B-ALL cells being killed over 3 days when co-cultured with human T-cells. Our pre-clinical data highlights the negative impact of an adipose-rich microenvironment on T-cell function and B-ALL immunogenicity, which subsequently compromises the efficacy of multiple classes of immunotherapies targeting CD19.
  • ||||||||||  Journal:  Functional Change of Effector Tumor-Infiltrating CCR5CD38HLA-DRCD8 T Cells in Glioma Microenvironment. (Pubmed Central) -  Nov 2, 2020   
    Higher CCL5 protein and mRNA levels were identified in glioma tissues, which was consistent with the immunohistochemistry results revealing both CCL5 and CD38HLA-DRCD8 T cell expression. Patients' CCR5CD38HLA-DRCD8 T cells were further validated and shown to display increases in CD45RACCR7 and T-bet accompanied by substantial CD107-a, IFN-γ, and Granzyme B levels in response to glioma cells.
  • ||||||||||  Journal:  Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery. (Pubmed Central) -  Oct 31, 2020   
    Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials.
  • ||||||||||  Yervoy (ipilimumab) / Ono Pharma, BMS
    Journal, PD(L)-1 Biomarker, IO Biomarker:  Dendritic Cell Vaccination in Metastatic Melanoma Turns "Non-T Cell Inflamed" Into "T-Cell Inflamed" Tumors. (Pubmed Central) -  Oct 30, 2020   
    A significant increase of CD8 TILs was found in post-vaccine biopsies of patients who were not previously treated with immune-modulating cytokines or Ipilimumab...However, the strength of the intratumoral T cell activation detected in post-DC therapy lesions is lessened by an occurring phenomenon of adaptive immune resistance, yet the concomitant PDL1 up-regulation. Overall, this study sheds light on DC immunotherapy-induced TME changes, lending the rationale for the design of smarter immune-combination therapies.
  • ||||||||||  Journal, PD(L)-1 Biomarker, IO Biomarker:  Allogeneic dendritic cells induce potent antitumor immunity by activating KLRG1CD8 T cells. (Pubmed Central) -  Oct 30, 2020   
    AlloDC could also treat mice with residual tumors and combination of anti-PD1 antibody could enhance this effects. Together, our study showed that alloDC-immunization could induce potent antitumor effect through the expansion of KLRG1CD8 T cells, which can work as both preventive and therapeutic tumor vaccines.
  • ||||||||||  Journal, IO Biomarker:  Expansion and CD2/CD3/CD28 stimulation enhance Th2 cytokine secretion of human invariant NKT cells with retained anti-tumor cytotoxicity. (Pubmed Central) -  Oct 30, 2020   
    Together, our study showed that alloDC-immunization could induce potent antitumor effect through the expansion of KLRG1CD8 T cells, which can work as both preventive and therapeutic tumor vaccines. These data establish a robust protocol to expand and novel pathways to enhance Th2 cytokine secretion and direct cytotoxicity in human iNKT cells, findings with direct implications for autoimmunity, vaccine augmentation and anti-infective immunity, cancer immunotherapy and transplantation.
  • ||||||||||  Journal:  Memory CD73+IgM+ B cells protect against Plasmodium yoelii infection and express Granzyme B. (Pubmed Central) -  Oct 30, 2020   
    Moreover, injection of enriched immune CD19+CD73+ B cells into nonimmune mice were significantly more protective against a PyNL infection than CD73- B cells. Interestingly, a substantial fraction of these CD73+ B cells also expressed IgM and granzyme B, a biomolecule that has been increasingly associated with protective responses against malaria.
  • ||||||||||  Journal, PD(L)-1 Biomarker, IO Biomarker:  Triple Therapy with MerTK and PD1 Inhibition plus Radiotherapy Promotes Abscopal Antitumor Immune Responses. (Pubmed Central) -  Oct 28, 2020   
    We provide novel evidence for a tissue-specific T-cell response predominated by Th1 cells and cytotoxic CD8+ T cells in ischaemic failing human hearts that may contribute to the progression of heart failure. The addition of α-PD1 + α-MerTK mAbs to radiotherapy could alter the cell death to be more immunogenic and generate adaptive immune response via increasing the retention of T cells in the tumor islets of the abscopal tumors which was proven to play a major role in survival of non-small cell lung cancer patients.
  • ||||||||||  Journal, IO Biomarker:  CTL-Derived Exosomes Enhance the Activation of CTLs Stimulated by Low-Affinity Peptides. (Pubmed Central) -  Oct 27, 2020   
    While exosome protein profiles vary significantly between early exosomes and their later-derived counterparts, both appear to have similar downstream functions. These results reveal a potential mechanism for fully activated CTLs in activating lower-affinity CTLs that may have important implications in boosting the function of low-affinity CTLs in immunotherapy for cancers and chronic viral infections.
  • ||||||||||  Journal, IO Biomarker:  Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria. (Pubmed Central) -  Oct 27, 2020   
    CD8 T cells were the main T cell subset expressing granzyme B. The proportion of granzyme B CD8 T cells was significantly higher in children with complicated malaria than in uncomplicated malaria, whereas the activation marker CD38 on CD8 T cells showed similar expression levels. This suggests a pathogenic role of cytotoxic CD8 T cells in the development of malaria complications in humans.
  • ||||||||||  Clinical, Journal, IO Biomarker:  IKZF1 polymorphisms are associated with susceptibility, cytokine levels, and clinical features in systemic lupus erythematosus. (Pubmed Central) -  Oct 26, 2020   
    In addition, significant relationships were observed between rs4917014 and susceptibility, granzyme B level, and hematological disorder in SLE (P = .005, P = .03 and P = .005, respectively).The results further support that IKZF1 may have an important role in the development and pathogenesis of SLE. Allele G of rs4132601 and rs4917014 is related to a decreased risk of SLE occurrence and associated with clinical features in SLE patients, including CD40 ligand level, granzyme B level, malar rash, and hematological disorder, which play important roles in disease progression.
  • ||||||||||  Journal:  The dietary peroxidized lipid, 13-HPODE, promotes intestinal inflammation by mediating granzyme B secretion from natural killer cells. (Pubmed Central) -  Oct 26, 2020   
    Results were recapitulated in 13-HPODE-fed mice, demonstrating both spatial and temporal patterns of elevated GZMB expression that favored acute treatments in the distal intestinal epithelium. Collectively, our results suggest that that HFD-derived POLs, like 13-HPODE, potentially contribute to intestinal inflammation by stimulating the secretion of pro-inflammatory granzymes by resident NK cells, ultimately revealing a more direct role for diet in modulating gut homeostasis and the immune environment.
  • ||||||||||  Journal:  Identification and Characterization of Circulating Naïve CD4+ and CD8+ T Cells Recognizing Nickel. (Pubmed Central) -  Oct 25, 2020   
    Moreover, naïve CD4+ T cells showed a polyclonal TCRβ composition and the presence of highly expanded clones with an enrichment and/or preferentially expansion of some TRBV genes that was donor and T-cell specific. Our results contribute to a better understanding of the mechanism of immunization to nickel and propose the T-cell priming assay as a useful tool to identify antigen-specific naïve T cells.
  • ||||||||||  Clinical, Journal:  Enhancing Immune Response and Heterosubtypic Protection Ability of Inactivated H7N9 Vaccine by Using STING Agonist as a Mucosal Adjuvant. (Pubmed Central) -  Oct 24, 2020   
    Furthermore, cGAMP induced significantly higher nucleoprotein specific CD4 and CD8 T cells responses in immunized mice, as well as upregulated the IFN-γ and Granzyme B expression in the lung tissue of mice in the early stages post a heterosubtypic virus challenge. These results indicated that STING agonist cGAMP was expected to be an effective mucosal immune adjuvant for pre-pandemic vaccines such as H7N9 vaccines, and the cGAMP combined nasal inactivated influenza vaccine will also be a promising strategy for development of broad-spectrum influenza vaccines.
  • ||||||||||  [VIRTUAL] The immune microenvironment in lower grade gliomas () -  Oct 24, 2020 - Abstract #SNO2020SNO_88;    
    Expression differences for cell surface and secreted proteins were confirmed in patient-derived tumor lines and functional relationships between altered chemokine expression and immune cell infiltration was investigated. Our data provide novel insights into the immune contexture of MAPK driven LGGs and suggest MAPK driven gliomas with biallelic inactivation of CDKN2A may be particularly vulnerable to immunotherapeutic modulation
  • ||||||||||  Review, Journal:  Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes. (Pubmed Central) -  Oct 23, 2020   
    Those findings underlie the possibility that impaired CD8 lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.