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- | Journal: Tertiary lymphoid structures show infiltration of effective tumor resident T cells in gastric cancer. (Pubmed Central) - May 11, 2021
Flow cytometry was performed to confirm the characteristics of CD103 CD8 T cells, and showed that CD103 CD8 T cells in GC expressed higher levels of PD-1, Granzyme B, and interferon-γ than CD103 CD8 T cells. Our results suggested that CD103 CD8 cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.
- || Clinical, Journal: PepFun: Open Source Protocols for Peptide-Related Computational Analysis. (Pubmed Central) - May 11, 2021
The package has been created under the python language based on built-in functions and methods available in the open source projects BioPython and RDKit. We present two tutorials where we tested peptide binders of the MHC class II and the Granzyme B protease.
- || CIGB-258 / Center for Genetic Engineering and Biotechnology
Clinical, Journal: CIGB-258, a peptide derived from human heat-shock protein 60, decreases hyperinflammation in COVID-19 patients. (Pubmed Central) - May 6, 2021
Altogether, these results support the therapeutic potential of CIGB-258 for diseases associated with hyperinflammation. Clinical trial registry: RPCEC00000313.
- | Journal: Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy. (Pubmed Central) - May 5, 2021
Levels of GrB in PBMC were higher if onconeural antibodies were detected. Tracking reactive immune responses, such as GrB in PBMC may have diagnostic and monitoring value in malignancy and PNS.
- | Journal: Nicotine exhausts CD8 T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B expression. (Pubmed Central) - May 5, 2021
We further validated that nicotine reduced granzyme B levels using a nuclear imaging technique, and demonstrated that nicotine exhausted peripheral blood mononuclear cells against HCC827 growth in the humanized tumor xenografts. This study demonstrated that nicotine exhausted CD8 T cells against HCC827 cells through increasing miR-629-5p to suppress IL2RB.
- abacavir / Generic mfg.
[VIRTUAL] Investigating the role of skin resident memory T-cells in a mouse model of DRESS () - May 4, 2021 - Abstract #SID2021SID_911;
A recently developed mouse model of DRESS employed C57BL/6 mice transgenically expressing human HLA-B*57:01 and treated with abacavir intraperitoneally (i.p.) and topically to induce ear dermatitis at the site of topical treatment...Taken together these data indicate that skin resident memory T cells develop as a result of drug/HLA specific DRESS-like dermatitis. We are currently testing whether these skin-resident memory T cells can mediate repeated episodes of DRESS-like dermatitis in response to drug, consistent with true drug allergy.
- KT-474 / Kymera Therap, Sanofi
[VIRTUAL] Multiple mediators of inflammation correlate with IRAK4 expression in the skin of Hidradenitis Suppurativa patients and are blocked by the IRAK4 protein degrader KT-474 in TLR-activated monocytes () - May 4, 2021 - Abstract #SID2021SID_907;
The upregulation of many of these same genes in human monocytes stimulated ex vivo with the TLR7/8 agonist R848 was blocked by KT-474, including IL-1β, TNF-α, IL-6, IL-8, NLRP3, PTGS2, CXCL2/3, IRF7, IFN-γ, IL- 2RA, granzyme B and perforin. These findings suggest a central role for IRAK4 in the pleiotropic inflammation in HS, and support the development of KT-474, currently in Phase 1 testing in healthy volunteers and patients with HS or AD.
- || Clinical, Journal, Myeloid-derived suppressor cells: CD8 T cells exhaustion induced by myeloid-derived suppressor cells in myelodysplastic syndromes patients might be through TIM3/Gal-9 pathway. (Pubmed Central) - May 4, 2021
Expression of Notch1, EOMES (associated with perforin and granzyme B secretion), p-mTOR and p-AKT (associated with cell proliferation) was decreased in CD8 T cells from MDS after co-culture with excess exogenous Gal-9. These suggested that MDSCs might be the donor of Gal-9, and TIM3/Gal-9 pathway might be involved in CD8 T cells exhaustion in MDS, and that TIM3/Gal-9 pathway inhibitor might be the promising candidate for target therapy of MDS in the future.
- | Journal: CD4 and CD8 T Cell Memory Interactions Alter Innate Immunity and Organ Injury in the CLP Sepsis Model. (Pubmed Central) - May 4, 2021
Both CD4 and CD8 memory T cells play important and independent roles in this response. These findings have profound implications for the development of murine models of human inflammatory disorders such as infection and sepsis.
- | Preclinical, Journal: Preclinical Evaluation of a Granzyme B PET Tracer for the Assessment of Immunotherapy Response. (Pubmed Central) - May 4, 2021
These findings have profound implications for the development of murine models of human inflammatory disorders such as infection and sepsis. No abstract available
- | Observational data, Journal: Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1. (Pubmed Central) - May 4, 2021
Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.
- || Vx-001 / Vaxon Biotech
Clinical, Journal, Tumor Mutational Burden, PD(L)-1 Biomarker, IO biomarker: Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC. (Pubmed Central) - May 1, 2021
These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1. These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors.
- [VIRTUAL] Assessment of Inflammatory and Neurodegenerative Biomarkers in NHPs with DRG Toxicity () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_889;
The data from this study suggest that these morphological effects do not lead to any notable changes in a panel of inflammatory cytokines and chemokines despite increased inflammatory cell infiltrate. Furthermore, the observed axonal degeneration was not associated with any classical biomarkers of neurodegeneration after 4 weeks.
- [VIRTUAL] Precise Tumor Targeting with NOT Logic-Gated Chimeric Antigen Receptor Gene Circuits () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_653;
NK cells can be used in an allogeneic fashion and can reduce cost and increase patient access relative to autologous products. Therapeutic cells with these NOT-gated CAR gene circuits may improve safety for currently validated cancer antigens, and also enable new therapies for previously unaddressed indications.
- [VIRTUAL] Engineered Type 1 Regulatory T Cells Have a Cytotoxic Profile and Kill Pediatric Acute Myeloid Leukemia Cells () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_652;
In conclusion, CD4IL-10 have a cytotoxic profile and can kill the majority of pAML blasts. Thus, CD4IL-10 is a novel cell therapy which could control GvHD and support GvL in pAML patients transplanted with allo-HSCT.
- | Journal, Cancer stem cells, IO biomarker: MUC1 plays an essential role in tumor immunity of colorectal cancer stem cell vaccine. (Pubmed Central) - Apr 29, 2021
Importantly, the CCSC vaccine has no toxic damage to organs. Overall, CCSC vaccine could serve as a potent and safe vaccine for CRC treatment, and MUC1 might play an essential role in CCSC vaccine.
- | Journal: Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4/CD8 T cells and humoral responses in macaques. (Pubmed Central) - Apr 29, 2021
In contrast, the cytotoxic marker expression by mucosal CD4 and CD8 T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4 T cells at the first line of defence, and cytotoxic CD4 and CD8 T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation.
- ||| Probably a good ol‘ Granzyme B+ T cell engaging #lungcancer (Twitter) - Apr 28, 2021
- | Journal: Non-apoptotic TRAIL function modulates NK cell activity during viral infection. (Pubmed Central) - Apr 28, 2021
In addition, TRAIL restricts NK1.1-triggered IFNγ production by NK cells. Our study reveals a hitherto unappreciated immunoregulatory role of TRAIL signaling on NK cells for the granzyme B-dependent elimination of antiviral T cells.
- || Clinical, Journal, Myeloid-derived suppressor cells: Increased myeloid-derived suppressor cells in patients with myelodysplastic syndromes suppress CD8+ T lymphocyte function through the STAT3-ARG1 pathway. (Pubmed Central) - Apr 28, 2021
Notably, targeting STAT3 pathway by selective inhibitor could decrease ARG1 expression in MDSCs and partially reverse the lower expression levels of effector molecules on CD8+ T lymphocytes. Therefore, this study revealed the potential STAT3-ARG1 mechanism behind MDSCs and provided a promising STAT3 targeting strategy in MDS.
- | Journal, PD(L)-1 Biomarker, IO biomarker: An aptamer-T cell targeted therapy for tumor treatment using sugar metabolism and click chemistry. (Pubmed Central) - Apr 27, 2021
Moreover, aptamer-T displayed even stronger anti-tumor effects than an anti-PD1 immune-checkpoint monoclonal antibody (mAb) treatment in mice and combination with anti-PD1 yielded synergic anti-tumor effects. This study uncovers the strong potential of the adoptive non-viral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application.
- | Journal: Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction. (Pubmed Central) - Apr 27, 2021
This study uncovers the strong potential of the adoptive non-viral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application. These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.
- | Journal: Long Non-coding RNA LINC02474 Affects Metastasis and Apoptosis of Colorectal Cancer by Inhibiting the Expression of GZMB. (Pubmed Central) - Apr 27, 2021
The findings revealed that a novel lncRNA, LINC02474, as an oncogene, could promote metastasis, but limit apoptosis partly by impeding GZMB expression in CRC. Besides, LINC02474 had the potential to be used as a biomarker in the prognosis of CRC.
- | Journal: Robust hepatitis B vaccine-reactive T cell responses in failed humoral immunity. (Pubmed Central) - Apr 27, 2021
Further studies are required to confirm their in vivo antiviral capacity. The ability to induce vaccine-reactive T cells paves new ways for improved vaccination and therapy protocols.
- | Journal, IO biomarker: Forest Bathing Always Makes Sense: Blood Pressure-Lowering and Immune System-Balancing Effects in Late Spring and Winter in Central Europe. (Pubmed Central) - Apr 24, 2021
In the winter, a slight activating and an interesting balancing effect regarding TIM-3 could be observed considering our finding that basal (pretest) TIM-3 expression by NK cells was significantly lower in the winter. Our work expands the knowledge on and potentials of forest medicine.
- dexamethasone / Generic mfg.
[VIRTUAL] Post-COVID-19 Hemophagocytic Lymphohistiocytosis in an Infant with Trisomy 21 () - Apr 23, 2021 - Abstract #CIS2021CIS_280;
She was treated with remdesivir, COVID-19 convalescent plasma, and dexamethasone...Etoposide and other immunosuppressive agents were held due to clinical improvement on dexamethasone alone...Bone marrow aspiration could distinguish the two disorders, but our patient had a negative aspiration, possibly due to partial treatment of her hemophagocytosis by her previous course of dexamethasone or bone marrow sampling error. Additionally, viruses, particularly Epstein-Barr virus, are well known triggers of hemophagocytic lymphohistiocytosis and this case demonstrates COVID-19 as a potential trigger as well.
- [VIRTUAL] Fluctuations in Quality of Life and Immune Responses During the Intravenous Immunoglobulin Infusion Cycles () - Apr 23, 2021 - Abstract #CIS2021CIS_223;
In addition, increases in quality of life and blood Tregs arose 1 week after infusion. The relationships between these observed perturbations remain to be elucidated in further studies.
- | Preclinical, Journal: Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection. (Pubmed Central) - Apr 23, 2021
Higher production of IL-17A, IFN-γ, IL-10, IP-10, GM-CSF, sFasL, Granzyme A, Granzyme B, Granulysin, and Perforin following infection positively correlated with HIV replication. These data show novel associations between MZB and NK cells and p24 production in RM and underscore the importance of inflammatory cytokines in mucosal HIV infection, demonstrating the likely critical role these innate immune responses play in early mucosal HIV replication in humans.
- | Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Biomarker, Retrospective data, Journal, Tumor microenvironment: Prognostic value of tissue-infiltrating immune cells in tumor microenvironment of follicular lymphoma: A meta-analysis. (Pubmed Central) - Apr 22, 2021
These data show novel associations between MZB and NK cells and p24 production in RM and underscore the importance of inflammatory cytokines in mucosal HIV infection, demonstrating the likely critical role these innate immune responses play in early mucosal HIV replication in humans. Multiple tissue-infiltratingimmune cells in microenvironment play critical and different roles in FL prognosis.
- | Journal, PD(L)-1 Biomarker, IO biomarker: Rhesus Cytomegalovirus-Specific CD8 Cytotoxic T Lymphocytes Do Not Become Functionally Exhausted in Chronic SIVmac239 Infection. (Pubmed Central) - Apr 20, 2021
Additionally, compared to SIVmac239-specific CTLs, greater proportions of RhCMV-specific CTLs were of the terminally differentiated effector memory phenotype (CD28 CCR7) during chronic SIVmac239 infection. These results suggest that, in contrast to SIVmac239-specific CTLs, RhCMV-specific CTLs maintain their phenotypes and cytolytic effector functions during chronic SIVmac239 infection, and that retargeting RhCMV-specific CTLs might be a promising SIV immunotherapeutic strategy.
- [VIRTUAL] Incidental Finding of Colorectal Cancer in a COVID-19 Patient, followed by Deep Profiling of SARS-CoV-2-associated Immune Landscape and Tumour Microenvironment () - Apr 20, 2021 - Abstract #CSIFCS2020CSI_FCS_52;
Our findings showed that, albeit after viral clearance, SARS-CoV-2 viral proteins were still detectable in various tissues, and that SARS-CoV-2-specific T cell responses could also be triggered. Our study highlights the complex interactions between cancer, COVID-19 and the immune system.
- nemvaleukin alfa (ALKS 4230) / Alkermes, Opdivo (nivolumab) / Ono Pharma, BMS
[VIRTUAL] Nemvaleukin alfa monotherapy in patients with advanced melanoma: ARTISTRY-1 () - Apr 18, 2021 - Abstract #EADOWCM2021EADO-WCM_683;
P1/2
Single-agent activity was observed among patients with melanoma who were previously treated with a CPI. Response criteria were met to expand the monotherapy melanoma cohort, and research of nemvaleukin among patients with advanced melanoma is ongoing.
- || Clinical, Clinical data, Journal, PD(L)-1 Biomarker, IO biomarker: Poor clinical outcomes and immunoevasive contexture in interleukin-9 abundant muscle-invasive bladder cancer. (Pubmed Central) - Apr 17, 2021
In conclusion, IL-9 cells infiltration could be applied as an independent prognosticator for clinical outcome and ACT/anti-PD-1 effectiveness. IL-9 cells infiltration diminished the cytotoxicity of CD8 T cells and NK cells resulting in tumor immune evasion, thus targeting IL-9 could be a potential therapeutic strategy for MIBC.
- | Journal, IO biomarker: Hypoxia enhances the production and antitumor effect of exosomes derived from natural killer cells. (Pubmed Central) - Apr 17, 2021
The hypoxia-treated NK92-Exo and NK92-hIL-15-Exo showed increased expression of three functional proteins of NK cells-specifically FasL, perforin, and granzyme B-as compared with their NK92-Exo counterparts exposed to normoxia. As an approach that supports overproduction of exosomes, hypoxic treatment of NK cells may serve as a promising therapeutic option for cancer immunotherapy.
- | Journal: White matter lesions in multiple sclerosis are enriched for CD20 CD8 tissue-resident memory T cells. (Pubmed Central) - Apr 16, 2021
- | decitabine / Generic mfg.
Journal: DNA hypomethylating agents increase activation and cytolytic activity of CD8 T cells. (Pubmed Central) - Apr 15, 2021
High-dimensional single-cell mass cytometry analyses reveal a selective effect of HMAs on a subset of human CD8 T cell subpopulations, increasing both the number and abundance of a granzyme B, perforin effector subpopulation. Overall, our findings support the use of HMAs as a therapeutic strategy to boost anti-tumor immune response.
- || Clinical, Journal: Peripheral Cytokine Levels Differ by HPV Status and Change Treatment-Dependently in Patients with Head and Neck Squamous Cell Carcinoma. (Pubmed Central) - Apr 14, 2021
Increased levels of pro-inflammatory cytokines in HPV+ compared to HPV- patients seem to reflect the elevated immunogenicity of HPV-positive tumors. High levels of HMGB1 and anti-inflammatory cytokines at recurrence may be interpreted as a sign of immune evasion.
- | Journal, IO biomarker: Expansion With IL-15 Increases Cytotoxicity of Vγ9Vδ2 T Cells and Is Associated With Higher Levels of Cytotoxic Molecules and T-bet. (Pubmed Central) - Apr 13, 2021
However, IL-2/IL-15-expanded Vγ9Vδ2 T cells showed higher levels of transcription factor T-bet expression, which could indicate that T-bet and cytotoxic molecule levels confer the increased cytotoxicity. These results advocate the inclusion of IL-15 into ex vivo Vγ9Vδ2 T cell expansion protocols in future clinical studies.
- | Journal, PD(L)-1 Biomarker, IO biomarker: Pulmonary endothelium-derived PD-L1 induced by the H9N2 avian influenza virus inhibits the immune response of T cells. (Pubmed Central) - Apr 10, 2021
These results advocate the inclusion of IL-15 into ex vivo Vγ9Vδ2 T cell expansion protocols in future clinical studies. Taken together, the results suggest that the H9N2 virus is able to inhibit the T cell immune response by upregulating PD-L1 expression in pulmonary microvascular endothelial cells.
- | Journal: Preparation and characterization of folic acid conjugated sulfated polysaccharides on NK cell activation and cellular uptake in HeLa cells. (Pubmed Central) - Apr 10, 2021
The binding capacity studies exposed the targeting ability of HeLa cells by folate receptor (FR) which was assessed by a confocal quantitative image cytometer analysis. These results indicate that SP-FA could be used as selective drug delivery systems for targeting FR-overexpressed cancer cells with less toxicity.
- || Clinical, Journal: T Cell Activation, Highly Armed Cytotoxic Cells and a Shift in Monocytes CD300 Receptors Expression Is Characteristic of Patients With Severe COVID-19. (Pubmed Central) - Apr 10, 2021
More importantly, correlation analysis showed a strong association between the alterations in the immune cells and the clinical signs of severity. These results indicate that patients with severe COVID-19 have a broad perturbation of their immune system, and they will help to understand the immunopathogenesis of COVID-19.
- Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] OBESITY ATTENUTATES T-CELL FUNCTION WHICH IMPACTS T-CELL IMMUNOTHERAPIES IN LYMPHOBLASTIC LEUKEMIA () - Apr 8, 2021 - Abstract #ASPHO2021ASPHO_66;
Adipocyte-secreted factors compromise the function of endogenous T-cells (in the presence and absence of Blinatumomab) and CAR T-cells. Given results demonstrating compromised T-cell function from obese pediatric patients with leukemia, our findings suggest that clinical assessments are necessary to determine if obesity reduces the efficacy of Blinatumomab and CAR T-cells in pediatric patients receiving treatment for lymphoblastic leukemia.
- | Journal, PD(L)-1 Biomarker, IO biomarker: A Microfluidic Platform for Single Cell Fluorometric Granzyme B Profiling. (Pubmed Central) - Apr 7, 2021
As proof of concept, we have shown the capability of a microfluidic platform to measure GrB production through a single cell enzymatic activity assay. Our platform might be a promising tool for evaluating the sensitivity of immunotherapies and identifying specific T cell subset responsible for the anti-tumor response.
- | Journal: Selective and potent CDK8/19 inhibitors enhance NK cell activity and promote tumor surveillance. (Pubmed Central) - Apr 7, 2021
The observed survival benefit was dependent on an intermittent treatment schedule of BI-1347, suggesting the importance of circumventing a hypo-responsive state of NK cells. These results suggest that CDK8/19 inhibitors can be combined with modulators of the adaptive immune system to inhibit the growth of solid tumors, independent of their activity on cancer cells, but rather through promoting NK cell function.
- | Journal: Differential Cytotoxic Function of Resident and Non-resident CD8+ T Cells in the Human Female Reproductive Tract Before and After Menopause. (Pubmed Central) - Apr 7, 2021
Finally, CD103+ T cells displayed reduced proliferation compared to CD103- T cells, but after proliferation, cytotoxic molecules were similar in each population. Our results highlight the complexity of regulation of cytotoxic function in the FRT before and after menopause, and are relevant to the development of protective strategies against genital infections and gynecological cancers as women age.
- | Journal: Beneficial Effect of Antibiotics and Microbial Metabolites on Expanded Vδ2Vγ9 T Cells in Hepatocellular Carcinoma Immunotherapy. (Pubmed Central) - Apr 7, 2021
Among the metabolites that we analyzed, 3-indopropionic acid (IPA) showed the highest concentration in antibiotic-treated mice and can improve the cytotoxic ability of γδT cells both in vitro and in vivo. Our research determined how the gut microbiota can influence the antitumor ability of γδT cells and identified potential intermediate molecules that connect the gut microbiota and γδT cells.
- | Preclinical, Journal: Foxp3 Regulatory T Cell Depletion after Nonablative Oligofractionated Irradiation Boosts the Abscopal Effects in Murine Malignant Mesothelioma. (Pubmed Central) - Apr 7, 2021
Our findings are applicable to the strategy of immuno-radiotherapy for generating optimal antitumor immune responses in the clinical setting. Targeting Tregs immediately after a short course of irradiation could have a major impact on the local response to irradiation and its abscopal effect.
- | Journal: Efficient Expansion of Human Granzyme B-Expressing B Cells with Potent Regulatory Properties. (Pubmed Central) - Apr 7, 2021
Finally, we found that expanded GZMB B cells exhibited a regulatory phenotype and were enriched in CD307b, CD258CD72, and CD21loPD-1 B cell subpopulations. Our study, to our knowledge, provides new insight into biology of GZMB B cells and an efficient method to expand GZMB B cells for future cell therapy applications.
- | Journal, IO biomarker: α-Pinene Enhances the Anticancer Activity of Natural Killer Cells via ERK/AKT Pathway. (Pubmed Central) - Apr 7, 2021
Furthermore, CT-26 colon cancer cells were allografted subcutaneously into BALB/c mice, and α-pinene treatment then inhibited allografted tumor growth. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.
- | Journal: New Method for the Expansion of Highly Purified Human Regulatory Granzyme B-Expressing B Cells. (Pubmed Central) - Apr 7, 2021
Their small proportion requires the development of expansion methods to enable their study and envision clinical applications. We describe here how to expand GZMB-expressing B cells to obtain more than 90% of highly purified GZMB B cells, and the protocol of B/T cells coculture for the evaluation of the suppressive function of the GZMB B-cell population.