- |||||||||| Critical roles of TIGIT+ human equivalent of B10 Bregs in immune regulation () - Apr 29, 2020 - Abstract #FOCIS2020FOCIS_111;
Moreover, the frequency of TIGIT+ Bregs correlated with that of CD25+CD127lo Tregs, while it inversely correlated with the frequency of follicular helper T cells. We thus concluded that TIGIT+ Bregs play essential roles in immune regulation.
- |||||||||| Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model. (Pubmed Central) - Apr 28, 2020
These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.
- |||||||||| Clinical, Journal: Clinicopathological features of primary central nervous system T-cell lymphomas (Pubmed Central) - Apr 28, 2020
PCNSL is uncommon, and most are B-cell lymphomas, while T-cell lymphomas are even rarer. As the latter may show atypical clinical manifestations, diverse histologic morphology and poor prognosis, early diagnosis and timely treatment are particularly important for patients to improve survival.
- |||||||||| Clinical, Journal: Increased circulating granzyme B in type 2 diabetes patients with low-grade systemic inflammation. (Pubmed Central) - Apr 27, 2020
Furthermore, multivariate linear regression analysis showed that increased GrB was associated with T2D diagnosis independently from possible confounders. In conclusion, our results show that increased levels of circulating GrB are associated with T2D diagnosis and correlates with markers of AT-linked systemic inflammation, suggesting a potential role for GrB in the inflammatory and reactive processes occurring in metabolic diseases.
- |||||||||| CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses (Board Number: P779) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_2307;
Collectively, this study demonstrated CD70 as a prominent regulator involved in immunosenescence, which led to defects and overwhelming inflammatory responses of T cells during aging. These findings provide a strong rationale for targeting CD70 to prevent dysregulation related to immunosenescence.
- |||||||||| Dissecting Human Tissue Resident Memory T cell Heterogeneity on the Single Cell Level (Board Number: P790) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_2300;
Importantly, these clusters show variable expression of genes coding for cytokines (IFNG, IL23A, IL26), transcription factors (TBX21, GATA3, BATF), and cytotoxic molecules (GNLY, GZMs), suggesting differentially regulated TRM subsets. Our results therefore highlight the heterogeneity of TRM across human tissue sites and define the transcriptional programming underlying TRM function.
- |||||||||| High-dimensional profiling of tumor-infiltrating CD4+T cells in Human cancer: Are they all tumor-specific? (Board Number: P1218) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1696;
Using in-vitroassay, we aim to confirm the presence of these bystander CD4+TILs specific for cancer-unrelated antigens (HCMV, EBV, Influenza). Overall, our findings could highlight that not all CD4+TILs are tumor-specific and could suggest measuring CD39 expression as a straightforward way to quantify or isolate tumor-specific T cells, thus opening new diagnostic and therapeutic avenues.
- |||||||||| The impact of the tumor microenvironment on granzyme production by CD8 T cells (Board Number: P1165) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1643;
The expression of different granzymes may have further implications for modulation of the TME through the form of cancer cell death induced, especially the increase in granzyme F which has been suggested to induce a more immunogenic form of cell death. Additionally, the impact of exhaustion on the cytotoxic activity of CD8 T cells from the TME may represent a means for exhausted CD8 T cells to regulate their cytotoxic activity by altering the granzymes they express.
- |||||||||| Amplification of neoantigen-specific antitumor responses using a long-lasting IL-2 fusion protein (Board Number: P1044) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1561;
The immune response within the tumor microenvironment was accompanied by increased frequencies of granzyme B-expressing CD4+ and CD8+ T cells. Our data show that limited application of high-dose IL-2/CD25 in the context of neoantigen vaccines offers potential advantages over IL-2 for melanoma treatment by avoiding toxicities seen with IL-2 therapy and minimizing Treg-associated tolerance.
- |||||||||| glucopyranosyl lipid A (G100) / Merck (MSD)
Role of NFKB signaling in Respiratory Epithelial Cells in Vaccine-Induced T Cell Immunity to Influenza (Board Number: P834) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1413;
We have identified a combination adjuvant consisting of acrylic acid polymers in a nanoemulsion (Adjuplex; ADJ) and TLR4 agonist (glucopyranosyl lipid adjuvant; GLA) that elicits potent CD8 and CD4 T cell responses in the respiratory tract...Greater percentages of effector CD8 T cells in NFKB-REC mice expressed KLRG-1, regardless of the adjuvant but effector CD8 T cells in GLA mice showed elevated levels of CX3CR1, CD49a and granzyme B following challenge with influenza A virus. Preliminary evidence suggests that vaccine-induced T cell-dependent protection against influenza virus might be impaired in NFKB-REC mice.
- |||||||||| low molecular weight dextran sulfate (ILB) / TikoMed
Toll-like receptor 7 protects against intestinal inflammation and restricts the development of tissue-resident memory CD8+ T cells (Board Number: P805) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1383;
Furthermore, Tlr7-/- mice were more susceptible to dextran sulfate sodium (DSS) colitis with more severe inflammation (Histoscore: WT: 7.6, Tlr7-/-: 12.7, p < 0.005), increased disease activity index (WT: 5.5, Tlr7-/-: 7.4, p < 0.05), and increased secretion of IFNg (WT: 5.2, Tlr7-/-: 24.2 ng/ml, p < 0.005) and TNFα (WT: 108.6, Tlr7-/-: 191.8 pg/ml, p < 0.05)...Our data shows that TLR7-deficiency promotes the development of LP Trm CD8+ T cells and increases susceptibility to DSS colitis. In conclusion, TLR7 plays an important role in maintaining immune response to intestinal viruses and protects against development of colitis.
- |||||||||| Vaccine elicited ASGM1+ CD8+ T cells are essential for protective immunity against Toxoplasma gondii infection. (Board Number: P756) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1335;
Recombinant IFNγ supplementation prolonged the survival of anti-ASGM1 treated mice, demonstrating that this antibody eliminated the protective T. gondii specific IFNγ-producing T cells important for control of the parasite. This study demonstrates that ASGM1 is enriched on effector T cells during T. gondii infection and the potential importance of changes in sialylation in lipid rafts for T cell activation during T. gondii infection.
- |||||||||| SIV and CD4 depletion distinctly reactivate latent Mycobacterium. tuberculosis infection (Board Number: P467) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1187;
PET CT imaging prior to treatment could predict reactivation in αCD4-treated animals, but not in SIV/Mtb animals. These data suggest that SIV infection disrupts protective immune responses against Mtb infection beyond the loss of CD4 T cells, and that synergy between SIV and Mtb occurs within granulomas.
- |||||||||| Increased NKG2D expressing NK cells in patients with chronic HBV infection (Board Number: P448) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1166;
The K562 target cell killing ability and IFN-gamma production correlated with the NKG2D expression, particularly in the HBV patients as compared to HCs. Conclusions Our study demonstrated that NK cells activity and status might play an important role in controlling HBV infection.
- |||||||||| Effect of combined low dose IL-2 and polyclonal Tregs infusion in Type 1 Diabetes patients (Board Number: P429) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_1150;
These data suggest that the usage of low-dose IL-2 together with polyclonal Tregs infusion exacerbate the expansion of Tregs but also of a GZMB+ CD8+ T cells and NK population already present in blood. Thus, the failure for all patients to maintain C-peptide level may be due to a shift of the immune balance toward activation rather than tolerance.
- |||||||||| Enhanced functional properties of in vitro expanded lymph node derived human NK cells (Board Number: P1337) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_888;
Lastly, LN derived NK cells also demonstrate enhanced cytolytic activity in vitro after expansion. Taken together our results suggest that in vitro expanded NK cells from LNs are potentially efficacious anti-tumor agents and could be leveraged for the development of future generation of NK cell directed immunotherapies.
- |||||||||| LB-100 / Lixte Biotech
Protein Phosphatase 2A (PP2A) is essential for CD8+ T cell mediated anti-tumor immunity (Board Number: P1156) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_754;
PP2A KO lead to lower AKT phosphorylation upon CD28 stimulation, along with lower proliferative capability of CD8+ T cells upon stimulation with anti-CD28 and suboptimal anti-CD3 concentration. Thus this study highlights the potentially important role of PP2A in CD8+ T cells and its therapeutic consideration for designing combinatorial immunotherapy.
- |||||||||| NF-kB1 induces T cell dysfunction to promote colon tumorigenesis (Board Number: P1182) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_735;
NF-kB1 has opposing functions in tumor cells and T cells in vivo. The p50 NF-kB represses Gzmb expression to confer colon tumor-infiltrating CTL a dysfunctional phenotype to promote colon tumor immune evasion, resulting in enhanced colon tumorigenesis and growth.
- |||||||||| Enhanced anti-tumor response upon deficiency of Msn kinase MINK1 in mice (Board Number: P1178) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_730;
Lower expression of exhaustion markers such as PD-1, TIM-3, and TIGIT were also observed in MINK1 KO CD8+ T cells. We are currently exploring the possible mechanisms of how MINK1 regulated CD8+ T cell function, and examine the possibility to target MINK1 in experimental tumor immunotherapy.
- |||||||||| Role of Granzyme B in mucosal immune responses. (Board Number: P867) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_519;
Interestingly, disease in recipients of grzB-/- T cells corresponded with increased IL-17+ CD4+ T cells in the mesenteric lymph nodes and colon lamina propria relative to recipients that received wt T cells. These data suggest that granzyme B functions in a protective manner during intestinal inflammation, possibly playing a role in T cell differentiation by holding generation of IL-17-producing T cells in check.
- |||||||||| Fine-tuning Notch expression by lymphocytic Granzyme B production (Board Number: P778) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_430;
These results show that the presence of GzmB can cause an alteration in the fine-tuning expression of Notch1. This work helps us understand the role of Granzyme B in Notch activation and differentiation of lymphocytes.
- |||||||||| Futhan (nafamostat) - Merck (MSD), Otsuka, Japan Tobacco, Nichi / Iko, U Tokyo
NATURAL KILLER CELL KILLING OF EXTRACELLULAR PSEUDOMONAS AERUGINOSA (Board Number: P473) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_267;
CRISPR knockout of granulysin or perforin in YT cells had no significant affect on NK cell killing of P. aeruginosa, as determined by CFU counts. Pre-treatment of YT and NK cells with the serine protease inhibitor 3,4-Dichloroisocoumarin (DCI) to inhibit granzymes, resulted in an inhibition of killing.
- |||||||||| rhIL-15 / National Cancer Institute
Differences in NK and Memory CD8 T cell responses to antigen-nonspecific stimulation by interleukin-15 (Board Number: P457) - Apr 25, 2020 - Abstract #IMMUNOLOGY2020IMMUNOLOGY_249;
Surprisingly, culture with rhIL-15 (10 ng/mL) for 4-6 days resulted in marked CD25 upregulation on CD56+CD3- NK cells but not bystander-activated CD45RA-CD95+ CD8 T cells (72±9.2% vs 11±3.8%, P=0.003) despite comparable expansion...Thus, although NK and bystander CD8 T cells can fill a similar immunologic niche regarding target cell killing, there are significant differences in expression of critical markers following activation. These differences may have consequences in the regulation of these cell types and impact anti-viral and anti-tumor responses.
- |||||||||| Clinical, Journal, IO Biomarker: Galectin-9 Expression Defines a Subpopulation of NK Cells with Impaired Cytotoxic Effector Molecules but Enhanced IFN-γ Production, Dichotomous to TIGIT, in HIV-1 Infection. (Pubmed Central) - Apr 23, 2020
Finally, we found that a cytokine mixture (IL-12, IL-15, and IL-18) can improve effector functions of Gal-9 NK cells in HIV-infected individuals, although, such an effect was observed for Gal-9 NK cells, as well. Overall, our data highlight the important role of Gal-9 in dysfunctional NK cells and, more importantly, a dichotomy for the role of Gal-9 versus TIGIT and suggest a potential new avenue for the development of therapeutic approaches.
- |||||||||| Journal: Human Tissue-Resident Mucosal-Associated Invariant T (MAIT) Cells in Renal Fibrosis and CKD. (Pubmed Central) - Apr 22, 2020
This work provides evidence that GZP PET imaging may be useful for rapid assessment of therapeutic efficacy in the context of clinical trials for both novel drugs as well as dosing regimens. Our findings indicate that human tissue-resident MAIT cells in the kidney may contribute to the fibrotic process of CKD via complex interactions with PTECs.
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