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- || Clinical, Journal: Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children. (Pubmed Central) - Aug 11, 2020
RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.
- | Journal: Involvement of MM cell-derived exosomes in T lymphocytes immune responses. (Pubmed Central) - Aug 11, 2020
TGF-β from MM-Treg decreased in the OPM2 and U266B1 groups when compared with the control group (P<0.05). MM-derived exosomes promote apoptosis and inhibit proliferation of HD-CD4+ T, inhibit apoptosis and promote proliferation, but inhibit perforin of HD-CD8+ T, inhibit apoptosis and promote proliferation HD-Treg, and inhibit perforin of MM-CD8+ T and TGF-β secretion of MM-Treg.
- || Clinical, Journal: Interleukin-35 suppresses antitumor activity of circulating CD8 T cells in osteosarcoma patients. (Pubmed Central) - Aug 8, 2020
MM-derived exosomes promote apoptosis and inhibit proliferation of HD-CD4+ T, inhibit apoptosis and promote proliferation, but inhibit perforin of HD-CD8+ T, inhibit apoptosis and promote proliferation HD-Treg, and inhibit perforin of MM-CD8+ T and TGF-β secretion of MM-Treg. The current data indicated that IL-35 contributed to CD8 T-cell dysfunction and limited antitumor immune response in osteosarcoma.
- | Journal: Differential effects of depleting versus programming tumor-associated macrophages on engineered T cells in pancreatic ductal adenocarcinoma. (Pubmed Central) - Aug 6, 2020
Thus, although functional modulation, rather than TAM depletion, enhanced the longevity of engineered T cells and increased tumor cell apoptosis, ultimately, anti-CD40 modulation was insufficient to rescue key effector defects in tumor-reactive T cells. This study highlights critical distinctions between how endogenous T cells that evolve in vivo, and engineered T cells with previously acquired effector activity, respond to modifications of the tumor microenvironment.
- | Journal: Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells. (Pubmed Central) - Aug 5, 2020
Moreover, we show that the nucleocapsid (N) protein from all examined orthohantaviruses are potential targets for caspase-3 and granzyme B. Recombinant N protein from ANDV, PUUV and the HFRS-causing Dobrava virus strongly inhibited granzyme B activity and also, to certain extent, caspase-3 activity. Taken together, this study demonstrates that six different orthohantaviruses inhibit apoptosis, suggesting this to be a general feature of orthohantaviruses likely serving as a mechanism of viral immune evasion.
- || Clinical, Journal: Neoadjuvant Radiochemotherapy Significantly Alters the Phenotype of Plasmacytoid Dendritic Cells and 6-Sulfo LacNAc Monocytes in Rectal Cancer. (Pubmed Central) - Aug 5, 2020
Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT tissues compared to pre-nRCT tumor specimens. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs, slanMo, and CD8 T cells, which may influence the clinical response of rectal cancer patients to nRCT.
- || Biomarker, Clinical, Journal: A parasite biomarker set for evaluating benznidazole treatment efficacy in patients with chronic asymptomatic Trypanosoma cruzi infection. (Pubmed Central) - Aug 4, 2020
The percentage of granzyme B/perforin CD8 T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%, p<0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8 T cells compared to that in the patients who did not meet the STEC.
- sirolimus / Generic mfg.
[VIRTUAL] Restoring Dysfunctional Regulatory T Cells Through Ex Vivo Expansion In Alzheimer Disease () - Aug 2, 2020 - Abstract #AAIC2020AAIC_2118;
Our data demonstrates that the ex vivo expansion of dysfunctional Tregs alters their immunophenotype and enhance their suppressive function at the Alzheimer disease stage. Restoration of regulatory T cell function could be explored as a means to modulate the inflammatory status of Alzheimer disease.
- | Journal, PD(L)-1 Biomarker, IO Biomarker: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity. (Pubmed Central) - Aug 1, 2020
Restoration of regulatory T cell function could be explored as a means to modulate the inflammatory status of Alzheimer disease. Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.
- | Journal, Myeloid-derived suppressor cells, IO Biomarker: Multidimensional imaging provides evidence for down-regulation of T cell effector function by MDSC in human cancer tissue. (Pubmed Central) - Jul 31, 2020
In these areas, the expression of effector molecules Granzyme B and Ki67 in T cells was strongly reduced, in particular for T cells that were in close proximity or physically engaged with PMN-MDSC, which expressed LOX-1 and arginase I. Patients with cancer with evidence for strong down-regulation of T cell function by PMN-MDSC had significantly impaired survival. In summary, our approach identifies areas of clinically relevant functional interaction between MDSC and T cells in human cancer tissue and may help to inform patient selection in future combination immunotherapies.
- || Clinical, Journal: Increased High-Risk Human Papillomavirus Viral Load Is Associated With Immunosuppressed Microenvironment and Predicts a Worse Long-Term Survival in Cervical Cancer Patients. (Pubmed Central) - Jul 31, 2020
Patients with increased HR-HPV viral load tend to be resistant to therapy with decreased immune surveillance in the immune microenvironment. Thus, HR-HPV viral load would influence the local immune microenvironment, and then further affect the survival of cervical cancer patients.
- | Journal: Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli. (Pubmed Central) - Jul 30, 2020
Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistant E. coli susceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance in E. coli.
- | Journal, Mismatch Repair: Mismatch Repair Status of Gastric Cancer and Its Association with the Local and Systemic Immune Response. (Pubmed Central) - Jul 29, 2020
Moreover, the prognostic effect of the preoperative systemic immune response status and TILs differed between the MSI-high (MSI-H) and non-MSI-H tumor groups. The present study may help to identify the mechanisms of cancer progression and develop treatment strategies for MSI-high gastric cancer.
- || ONC201 / Chimerix
Clinical, Journal: Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. (Pubmed Central) - Jul 29, 2020
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The present study may help to identify the mechanisms of cancer progression and develop treatment strategies for MSI-high gastric cancer. Weekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation.
- | Preclinical, Journal, IO Biomarker: Discovery of a novel natural killer cell line with distinct immunostimulatory and proliferative potential as an alternative platform for cancer immunotherapy. (Pubmed Central) - Jul 29, 2020
Weekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation. NK101 is a unique NK cell line bearing strong immunostimulatory potential and substantial scalability, providing an attractive source for adoptive cancer immunotherapy.
- | Journal, IO Biomarker: Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes. (Pubmed Central) - Jul 29, 2020
IFN-I induces STAT3 activation to activate Gzmb expression to enhance CTL effector function to suppress tumor development. Human colorectal carcinoma may use down-regulation of IFNAR1 on CTLs to suppress CTL effector function to evade host cancer immunosurveillance.
- | Journal, PD(L)-1 Biomarker, IO Biomarker: Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combination. (Pubmed Central) - Jul 29, 2020
Furthermore, 3x8Gy was the most effective protocol when associated with anti-PD-L1 and anti-TIGIT. This is the first study combining RT and anti-TIGIT with promising results; further studies are warranted.
- | Journal, IO Biomarker: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells. (Pubmed Central) - Jul 29, 2020
Taken together, these results indicated that IL-27 can synergize on NK cell expansion and activation with IL-15 and IL-18. In addition, we described an improved culture method for ex vivo expansion of human NK cells with IL-15/IL-18/IL-27 stimulation and characterized the response of NK cells to this stimulation.
- | Journal, Cancer stem cells, IO Biomarker: T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells. (Pubmed Central) - Jul 29, 2020
In addition, we described an improved culture method for ex vivo expansion of human NK cells with IL-15/IL-18/IL-27 stimulation and characterized the response of NK cells to this stimulation. Our findings demonstrated that NKG2D CAR-T cells targeted glioblastoma cells and cancer stem cells in an NKG2D-dependent manner, supporting the use of CAR-T therapy in glioblastoma therapeutic strategies.
- | Keytruda (pembrolizumab) / Merck (MSD)
Biomarker, Journal, Tumor microenvironment, PD(L)-1 Biomarker, IO biomarker: Development of an Adrenocortical Cancer Humanized Mouse Model to Characterize Anti-PD1 Effects on Tumor Microenvironment. (Pubmed Central) - Jul 29, 2020
Our findings demonstrated that NKG2D CAR-T cells targeted glioblastoma cells and cancer stem cells in an NKG2D-dependent manner, supporting the use of CAR-T therapy in glioblastoma therapeutic strategies. Our study reports the first humanized ACC PDX mouse model which may be useful to define mechanisms and biomarkers of response and resistance to immune-based therapies, to ultimately provide more personalized care for patients with ACC.
- | Preclinical, Journal: Therapy with multi-epitope virus-like particles of B19 parvovirus reduce tumor growth and lung metastasis in an aggressive breast cancer mouse model. (Pubmed Central) - Jul 29, 2020
Only treatments with multi-epitope virus-like particles induced specific proliferative responses of CD8 and CD4 T lymphocytes and Granzyme-B production in lymphatic nodes local to the tumor. Treatment with recombinant multiple neoepitopes-virus-like particles induced specific cellular responses, inhibited tumor growth and macro-metastasis, thus B19-virus-like particles may function as an effective delivery system for neoepitopes for personalized immunotherapy.
- | Preclinical, Journal, IO Biomarker: Nobiletin and related polymethoxylated flavones bind to and inhibit the nuclear export factor Exportin-1 in NK leukemia cell line KHYG-1. (Pubmed Central) - Jul 29, 2020
PMFs also induced the nuclear retention of the tumor suppressor protein p53, a known XPO1 cargo protein, resulting in KHYG-1 cell cycle arrest. Collectively, these results suggest that PMFs modulate KHYG-1 function, at least in part, by inhibiting XPO1.
- || Clinical, Journal: Association of Perforin and Granzyme-B Levels with Hyperandrogenism in Polycystic Ovary Syndrome: A Case-Control Study. (Pubmed Central) - Jul 29, 2020
Collectively, these results suggest that PMFs modulate KHYG-1 function, at least in part, by inhibiting XPO1. The results of present study together with evidences about the release of pro-inflammatory cytokines in insulin resistance, CVD and PCOS suggest that perforin/granzyme-B may be involved in interactions of sex hormones system in PCOS patients.
- | Biomarker, Journal, PD(L)-1 Biomarker, IO Biomarker: F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer. (Pubmed Central) - Jul 25, 2020
The results of present study together with evidences about the release of pro-inflammatory cytokines in insulin resistance, CVD and PCOS suggest that perforin/granzyme-B may be involved in interactions of sex hormones system in PCOS patients. This study introduces MMVR as a new imaging biomarker and its ability to noninvasively capture increased PD-L1 tumour expression and predict clinical benefit from checkpoint blockade in NSCLC should be further evaluated.
- | Journal: The Effects of Mesenchymal Stem Cells on Antimelanoma Immunity Depend on the Timing of Their Administration. (Pubmed Central) - Jul 24, 2020
In summing up, the timing of MSC administration into the tumor microenvironment was crucially important for MSC-dependent modulation of antimelanoma immunity. MSCs transplanted during the initial phase of melanoma growth exerted tumor-suppressive effect, while MSCs injected during the progressive stage of melanoma development suppressed antitumor immunity and enhanced tumor expansion.
- || Clinical, Journal: Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients. (Pubmed Central) - Jul 24, 2020
Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality. While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.
- || Clinical, Journal: A Randomized Controlled Study to Evaluate the Safety and Reactogenicity of a Novel rVLP-Based Plant Virus Nanoparticle Adjuvant Combined with Seasonal Trivalent Influenza Vaccine Following Single Immunization in Healthy Adults 18-50 Years of Age. (Pubmed Central) - Jul 24, 2020
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The Papaya Mosaic Virus adjuvant in doses of 30 to 240 µg combined with reduced influenza antigen content was safe with no signals up to 3 years after vaccination. A dose-related adjuvant effect was observed and immunogenicity results suggest that efficacy study should be conducted in influenza antigen-naïve participants.
- [VIRTUAL] Predicting response to checkpoint inhibitors using complex molecular characteristic and immunoprofiling in solid tumours (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_1843;
Funding: Ministry of Health of the Czech Republic, grant nr. NV18-03-00339.
- | Journal: Toward more accurate prediction of caspase cleavage sites: a comprehensive review of current methods, tools and features. (Pubmed Central) - Jul 22, 2020
Furthermore, we experimentally validate the predictions of a case study by performing caspase cleavage assay. We anticipate that this comprehensive review and survey analysis will provide an insightful resource for biologists and bioinformaticians who are interested in using and/or developing tools for caspase/granzyme B cleavage prediction.
- | Journal: Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival. (Pubmed Central) - Jul 22, 2020
miR-885-5p could favor cell survival in OT by diminishing the levels of CRADD/RAIDD and CASP3. Nonetheless, given the nature of any complex phenomenon in humans, only cumulative data will help to determine whether this microRNA differential profile may be related to the cause or consequence of operational tolerance.
- || Biomarker, Clinical, Journal, PD(L)-1 Biomarker, IO biomarker: High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer. (Pubmed Central) - Jul 22, 2020
Its prognostic utility is independent of PD-L1 and other common markers of immune activation. High OX-40 expression potentially identifies a unique subgroup of NSCLC that may benefit from co-stimulation with OX-40 agonist antibodies and potentially enhance the efficacy of existing immune checkpoint therapies.
- | Journal, PD(L)-1 Biomarker, IO Biomarker: High expression of B7-H3 on stromal cells defines tumor and stromal compartments in epithelial ovarian cancer and is associated with limited immune activation. (Pubmed Central) - Jul 22, 2020
We also find that some but not all immune parameters show consistency between peritoneal metastatic sites. These data have implications for the design of immunotherapies targeting these B7 molecules in epithelial ovarian cancer.
- [VIRTUAL] Characterization of immunoreactivity with whole-slide imaging and digital analysis in high-grade serous ovarian cancer (On-Demand) - Jul 21, 2020 - Abstract #ESMO2020ESMO_1099;
Legal entity responsible for the study: The authors. Funding: Has not received any funding.
- | Journal: Granzyme B cleaves multiple HSV-1 and VZV gene products and VZV ORF4 inhibits Natural Killer cell dependent cytotoxicity. (Pubmed Central) - Jul 21, 2020
Unlike HSV-1, VZV only infects humans and there are limited model systems, thus little is known concerning how VZV maintains latency and why VZV reactivates. Through studying the link between immune cell cytotoxic functions, granzyme B and viral gene products an increased understanding of viral pathogenesis will be achieved.
- | Journal: Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity. (Pubmed Central) - Jul 21, 2020
Likewise, the MLK3 inhibitor in pan T cells, isolated from breast cancer patients, also increases cytotoxic CD8 T cells. These results collectively demonstrate that MLK3 plays an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer.
- | Journal, IO Biomarker: Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression. (Pubmed Central) - Jul 19, 2020
Moreover, Tim-3 signaling reduced the perforin and granzyme B expression of Vγ9Vδ2 T cells in an ERK1/2 signaling pathway-dependent manner. This knowledge reveals that Tim-3 may be a promising therapeutic target to improve Vγ9Vδ2 T cell-based adoptive immunotherapy for colon cancer.
- || Clinical, Journal, IO Biomarker: The modulatory activity of T cell immunoglobulin and mucin domain-containing protein 3 on T lymphocytes in patients with chronic heart failure (Pubmed Central) - Jul 19, 2020
The relative mRNA expression levels of perforin and granzyme B also increased (all P<0.05). TIM-3 was increasingly expressed in T cells from patients with chronic heart failure, and might take part in the regulation of T cell dysfunction in chronic heart failure.
- | Journal: Impaired NK cell activation during acute dengue virus infection: A contributing factor to disease severity. (Pubmed Central) - Jul 17, 2020
To summarize, our study reports, that efficient NK cell response during acute phase of DENV infection is crucial for preventing severity of the disease. This study helps in understanding the dynamics of NK cell response in immunopathogenesis of DENV infection; which is crucial for development of efficacious therapeutics as well as vaccine.
- | Journal, Myeloid-derived suppressor cells: Myeloid Derived Suppressor Cells Depletion May Cause Pregnancy Loss via Upregulating the Cytotoxicity of Decidual Natural Killer Cells. (Pubmed Central) - Jul 16, 2020
This study helps in understanding the dynamics of NK cell response in immunopathogenesis of DENV infection; which is crucial for development of efficacious therapeutics as well as vaccine. Depletion of MDSCs may cause pregnancy loss, while upregulating the cytotoxicity of decidual NK cells and increasing NKreg and Treg cell numbers.
- | Journal: CD49a regulates the function of human decidual natural killer cells. (Pubmed Central) - Jul 16, 2020
CD49a is involved in the regulation of dNK cells functions, including cytotoxic activity, migration, and adhesion. Further, lnc-49a is a positive regulator of CD49a in human primary dNK cells.
- | Journal: Transcriptional Profiles of California Sea Lion Peripheral NK and CD T Cells Reflect Ecological Regionalization and Infection by Oncogenic Viruses. (Pubmed Central) - Jul 16, 2020
Our study is a first approach to profile the transcriptional patterns of key immune effectors of free-ranging California sea lions and their association with ecological regions and oncogenic viruses. The observed results add insight to our understanding of immune competence of marine mammals, and may help elucidate the marked difference in the number of cases of urogenital carcinoma in sea lions from US waters and other areas of their distribution.
- | Journal: Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation. (Pubmed Central) - Jul 16, 2020
T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation.
- | infigratinib (BGJ398) / BridgeBio, Pfizer, Lenvima (lenvatinib) / Eisai, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen
Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO Biomarker: Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma. (Pubmed Central) - Jul 11, 2020
Inhibition of vascular endothelial growth factor receptor and FGFR augmented the efficacy of anti-PD-1 antibodies. Combined lenvatinib/anti-PD-1 treatment appears to exert antitumor activity by synergistically modulating effector T cell function in the TME and by mutually regulating tumor vessel normalization.
- | Journal, CAR T-Cell Therapy, PD(L)-1 Biomarker, IO Biomarker: Interleukin-23 engineering improves CAR T cell function in solid tumors. (Pubmed Central) - Jul 9, 2020
In comparison to CAR T cells, p40-Td CAR T cells showed improved antitumor capacity in vitro, with increased granzyme B and decreased PD-1 expression. In two xenograft and two syngeneic solid tumor mouse models, p40-Td CAR T cells showed superior efficacy in comparison to CAR T cells and attenuated side effects in comparison to CAR T cells expressing IL-18 or IL-15.
- || Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification. (Pubmed Central) - Jul 9, 2020
However, the hrHPV-positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV-negative tumors (p = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.
- | Journal: Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology. (Pubmed Central) - Jul 7, 2020
Melanoma patients who developed immune-related adverse events under immune checkpoint CIT also presented with expanded granzyme-expressing CD4+ and CD8+ T cell populations. Our data suggest that acute infections may induce immunopathology in patients treated with CIT, and that effective measures for infection prevention should be applied.
- [VIRTUAL] Pulmonary Artery Endothelial Cells Are Sex Dimorphic in Their Proliferative Potential. Implications for Plexiform Arteriopathy (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_1797;
Conclusion. Thus, Xist/MEF2/KLF2 axis may explain the pulmonary artery ECs' sexual dimorphism in the proliferative response.
- | Journal, PD(L)-1 Biomarker, IO Biomarker: PD-1 Expression and Function of T-Cell Subsets in TILs From Human Lung Cancer. (Pubmed Central) - Jul 5, 2020
We found that higher interferon-γ and granzyme B production in CD4/CD8PD-1T-cell subsets in TILs than in peripheral blood mononuclear cells (PBMCs); except for PD-1Tscm, higher tumor necrosis factor-α production was observed in PD-1T-cell subsets in TILs than in PBMCs; the expression level of interleukin-17 were lower in PD-1T cells in TILs than in PBMCs; and perforin expression was significantly reduced in CD4PD-1T cells subsets in TILs compared with peripheral blood. Clarify elucidating the composition and function of PD-1T-cell subsets in TILs will have great value in clinical application for evaluating the sensitivity to PD-1 blockade and selecting the promising candidate T-cell subsets in TILs for combination immunotherapy in human lung cancer.
- | Journal: A shift toward inhibitory receptors and impaired effector functions on NK cells contribute to immunosuppression during sepsis. (Pubmed Central) - Jul 4, 2020
We found that the proportion of NK cells in lymphocytes was negatively associated with patient 28 d death in septic patients. Phenotypic changes of a shift toward inhibitory receptors and impairment of effector functions of NK cells might be an important mechanism of immunosuppression during sepsis.
- | Journal: Extended cleavage specificities of two mast cell chymase-related proteases and one granzyme B-like protease from the platypus, a monotreme. (Pubmed Central) - Jul 3, 2020
This suggests that MC chymotryptic enzymes have been conserved, both in structure and extended cleavage specificity, for more than 200 million years, indicating major functions in MC-dependent physiological processes. We have also studied a third closely related protease, originating from the same chymase locus whose cleavage specificity is closely related to the apoptosis-inducing protease from cytotoxic T cells, granzyme B. The presence of both a chymase and granzyme B in all studied mammals indicates that these two proteases bordering the locus are the founding members of this locus.