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- | Journal, IO Biomarker: CD4(+) CD28(null) T Cells Are Not Alloreactive Unless Stimulated by IL-15. (Pubmed Central) - Apr 11, 2019
Finally, CD4(+) CD28(null) T cells did not show significant suppression. Thus, CD4(+) CD28(null) T cells represent a population with absent alloreactivity unless IL-15 is present.
- | Journal: Associations of Simian Immunodeficiency Virus (SIV)-Specific Follicular CD8T Cells with Other Follicular T Cells Suggest Complex Contributions to SIV Viremia Control. (Pubmed Central) - Apr 11, 2019
In contrast, in HVL macaques, Tfreg and fCD8 cell frequencies tended to be negatively correlated, and a positive correlation was seen between Tfreg number and viremia, suggesting possible dysfunction and suppression of an effective fCD8 cell immune response. Our data suggest that control of virus-infected cells in B cell follicles not only depends on fCD8 cell cytotoxicity but also on complex fCD8 cell associations with Tfh cells and Tfreg.
- | Journal: Differential impact of T-bet and IFNγ on pancreatic islet allograft rejection. (Pubmed Central) - Apr 11, 2019
Anti-islet T cell responses require T-bet but not IFNγ-dependent programs. Our results provide new clues on the mechanisms dictating islet rejection and may help refining the therapeutic/immunosuppressive regimens applied in diabetic patients receiving islets or pancreas allografts.
- | Clinical, Journal, IO biomarker: Rare case of low-grade extranodal NK/T-cell lymphoma, nasal type, arising in the setting of chronic rhinosinusitis and harboring a novel N-terminal KIT mutation. (Pubmed Central) - Apr 11, 2019
Our case of ENKTCL-NT is unusual due to (1) an indolent clinical course (2) low-grade histopathologic features including a low proliferative index (3) lack of CD56 expression and (4) a novel KIT mutation. This case raises awareness of the existence of a subset of cases of ENKTCL-NT that can potentially be misdiagnosed as a reactive process, particularly in patients with recurrent chronic rhinosinusitis.
- | Clinical, Journal: Tissue-resident Eomes NK cells are the major innate lymphoid cell population in human infant intestine. (Pubmed Central) - Apr 11, 2019
Absolute intestinal NK cell numbers decrease gradually during the first year of life, coinciding with an influx of intestinal Eomes T cells; by contrast, epithelial NKp44CD69 NK cells with less cytotoxic capacity persist in adults. In conclusion, NK cells are abundant in infant intestines, where they can provide effector functions while Eomes T cell responses mature.
- | Journal, IO Biomarker: Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells. (Pubmed Central) - Apr 9, 2019
In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.
- | methionine enkephalin (IRT-101) / Immune Therap
Journal, PD(L)-1 Biomarker, IO Biomarker: Rules to activate CD8T cells through regulating subunits of opioid receptors by methionine enkephalin (MENK). (Pubmed Central) - Apr 9, 2019
In addition, non-selectively blocking both MOR and DOR by NTX could further impair the functions and proliferation of CD8T cells. Our currently data indicated that MENK could play a vital role in immune functions via precise regulation to subunits of opioid receptors.
- | Preclinical, Journal: In vitro studies on anti-inflammatory activities of kiwifruit peel extract in human THP-1 monocytes. (Pubmed Central) - Apr 9, 2019
Our currently data indicated that MENK could play a vital role in immune functions via precise regulation to subunits of opioid receptors. The reported findings demonstrated a strong and broad anti-inflammatory profile of the kiwifruit peel extract, which makes it a promising preventive and therapeutic natural ingredient for nutraceutical, cosmetic and pharmaceutical formulations to counteract multiple inflammatory disorders.
- | Journal: Remodeling of secretory lysosomes during education tunes functional potential in NK cells. (Pubmed Central) - Apr 9, 2019
Furthermore, inhibition of PI(3,5)P synthesis, or genetic silencing of the PI(3,5)P-regulated lysosomal Ca-channel TRPML1, leads to increased granzyme B and enhanced functional potential, thereby mimicking the educated state. These results indicate an intrinsic role for lysosomal remodeling in NK cell education.
- | Journal: Early effector maturation of naïve human CD8 T cells requires mitochondrial biogenesis. (Pubmed Central) - Apr 5, 2019
Inhibition of early mitochondrial biogenesis diminished mROS dependent IL-2 production - as well as subsequent IL-2 dependent TNF, IFN-?, perforin, and granzyme B production. Together, these findings point to the importance of mitochondrial biogenesis during early effector maturation of CD8 T cells.
- | Journal: Blimp-1 induces and Hobit maintains the cytotoxic mediator granzyme B in CD8 T cells. (Pubmed Central) - Apr 5, 2019
Notably, Blimp-1 was required for expression of granzyme B in murine effector T cells and Trm, while Hobit specifically regulated granzyme B in murine Trm during the memory phase. These findings suggest that Blimp-1 initiates cytotoxic effector function and that Hobit maintains cytotoxicity in a deployment-ready modus in Trm.
- | Journal: Effect of sulfation and partial hydrolysis of polysaccharides from Polygonatum sibiricum on immune-enhancement. (Pubmed Central) - Apr 5, 2019
RAW264.7 cells appeared to be activated via MR and TLR4 mediated signaling pathway, but CR3 and TRL2 might play a main role in stimulating NK cells. Overall, the present study suggests the potential application of polysaccharides from P. sibiricum in functional foods and pharmacological industries.
- | cisplatin / generics
Journal, Myeloid-derived suppressor cells: Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells. (Pubmed Central) - Apr 5, 2019
Mechanistic study showed that carnosic acid treatment boosted the function of CD8 T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8 T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.
- Opdivo (nivolumab) / Ono Pharma, BMS
Control of progressive multifocal leukoencephalopathy by programmed cell death protein-1 blockade (HALL F) - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_4251;
In this patient nivolumab blockade of the PD-1/PDL-1 axis led to control of JCV replication, radiological IRIS and clinical improvement. Immune checkpoint blockade by re-invigorating exhausted immune cells represents a potential relevant strategy for treating PML.
- Mucosal-associated invariant T cells exhibit an activated and cytotoxic profile in patients with recurrent urinary tract infection () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_3239;
This suggests that MAIT cells are involved in the defense against uropathogens. Currently it is unclear whether MAIT cells are able to migrate to the urogenital tract or whether also (lower) UTI may be accompanied by ascending bacteria and bacterial metabolites, which would lead to activation of MAIT cells in the bloodstream.
- | Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma. (Pubmed Central) - Apr 4, 2019
These altered immune cell profiles were clinically relevant as they were accompanied by significantly reduced tumor growth. Our study suggests that blocking LDH-A in the tumor might improve the efficacy of anti-PD-1 therapy.
- | Rituxan (rituximab) / Roche, Biogen
Journal: Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation. (Pubmed Central) - Mar 29, 2019
This study reports significant decreases in NK cell lysis and a significant increase in NK cell degranulation following Rituximab incubation in vitro in CFS/ME patients, suggesting Rituximab may be toxic for NK cells. Caution should be observed in clinical trials until further investigations in a safe and controlled in vitro setting are completed.
- | Preclinical, Journal: Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice. (Pubmed Central) - Mar 28, 2019
However, alcohol consumption decreased the expression of perforin in spleen and liver. Taken together, chronic alcohol consumption exacerbates cytomegalovirus infection via impairing non-specific and specific NK cell activation, specifically IFN-γ and perforin production.
- | Clinical, Journal: The Cytomegalovirus-Specific IL-21 ELISpot Correlates with Allograft Function of Kidney Transplant Recipients. (Pubmed Central) - Mar 27, 2019
IL-21, a cytokine involved in aging that is secreted by activated CD4+ T cells, may also impact on allograft function. Thus, the CMV-specific IL-21 ELISpot could become a new tool to assess if CMV seropositivity represents a hazard for the graft.
- | Preclinical, Journal: Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation. (Pubmed Central) - Mar 27, 2019
These data define microenvironmental IL-1β as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1β facilitates checkpoint inhibition.
- | Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche
Clinical, Journal, IO Biomarker: Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer. (Pubmed Central) - Mar 25, 2019
By combination treatment with rhCD137L, similar effects were obtained regarding cancer cell cytotoxicity in the presence of cetuximab (p < 0.01)...These results confirmed that FcγRIIIA polymorphisms (158 V/V) enhanced CD137 expression to a greater degree than 158 F polymorphisms (p = 0.014). Our results suggested that CD137 stimulation could promote the effects of tumor-targeting mAbs in gastric cancer, and that further investigation of antibody binding affinity and in vivo activities might improve therapeutic strategies related to the treatment of gastric cancer patients.
- | Review, Journal: Chemokines and cancer: new immune checkpoints for cancer therapy. (Pubmed Central) - Mar 23, 2019
We observed that one of the four CCR8 ligands, CCL1, produced by these cells, potentiates their suppressive activity via induction of CCR8, FOXp3, CD39, Granzyme-B, and IL-10 in a positive feedback mechanism, making them master drivers of immune regulation. Collectively, this suggests blocking the CCR8-CCL1 interaction, alone or combined with other immune checkpoint inhibitors, as an approach to treat malignant diseases.
- | Journal: Immune signatures for HIV-1 and HIV-2 induced CD4T cell dysregulation in an Indian cohort. (Pubmed Central) - Mar 21, 2019
Lower immune activation in these individuals indicates that persistent immune activation driven CD4T cell depletion, as observed in untreated HIV-1 infected individuals, may not be as severe and provides evidence for a disparate pathogenesis mechanism. Our work also supports novel immunomodulatory therapeutic strategies for both HIV-1 and HIV-2 infection.
- | Anktiva (inbakicept) / NantWorks
Journal: An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell-cytotoxic function from TGF-β1-mediated immunosuppression. (Pubmed Central) - Mar 2, 2019
An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies...IL-15SA/IL-15RA blocked Smad2/3-induced transcription, resulting in the rescue of NK cell-cytotoxic function from TGF-β1-induced suppression. These findings suggest that in addition to increasing NK cell function via promoting the IL-15 signaling pathway, IL-15SA/IL-15RA can function as an inhibitor of TGF-β1 signaling, providing a potential remedy for NK cell dysfunction in the immunosuppressive tumor microenvironment.
- | Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: N-acetyl cysteine protects anti-melanoma cytotoxic T cells from exhaustion induced by rapid expansion via the downmodulation of Foxo1 in an Akt-dependent manner. (Pubmed Central) - Mar 2, 2019
Pharmacological inhibition of the PI3K/Akt pathway ablates the decrease in Foxo1 induced by NAC treatment of activated T cells. This suggests a model in which NAC through PI3K/Akt activation suppresses Foxo1 expression, thereby impacting its transcriptional targets EOMES, PD-1, and granzyme B. Taken together, our results indicate that NAC exerts pleiotropic effects that impact the quality of TCR-transduced T cells and suggest that the addition of NAC to current clinical protocols should be considered.
- | Anktiva (inbakicept) / NantWorks
Journal, PD(L)-1 Biomarker, IO biomarker: The multi-functionality of N-809, a novel fusion protein encompassing anti-PD-L1 and the IL-15 superagonist fusion complex. (Pubmed Central) - Feb 5, 2019
This molecule comprises the IL-15/IL15Rα superagonist complex containing the Fc-domain of IgG1 (N-803, formerly designated as ALT-803) fused to two single chain anti-PD-L1 domains...Similarly, the highest level of ADCC was seen when both NK cells (from donors or cancer patients) and tumor cells were exposed to N-809. These studies thus demonstrate the multi-functionality of this novel agent.
- | Journal: Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response. (Pubmed Central) - Jan 5, 2019
These studies thus demonstrate the multi-functionality of this novel agent. The IRF-1 priming of TEXs enhances antitumour immune response.British Journal of Cancer advance online publication, 7 November 2017; doi:10.1038/bjc.2017.389 www.bjcancer.com.
- | Preclinical, Journal: EGFR and CD44 Dual-Targeted Multifunctional Hyaluronic Acid Nanogels Boost Protein Delivery to Ovarian and Breast Cancers in Vitro and in Vivo. (Pubmed Central) - Dec 16, 2018
Intriguingly, the therapeutic studies in SKOV-3 human ovarian carcinoma and MDA-MB-231 human breast tumor xenografted in nude mice revealed that GrB-EGFR/CD44-NGs at a low dose of 3.85 nmol GrB equiv./kg induced nearly complete growth suppression of both tumors, which was obviously more effective than GrB-CD44-NGs, without causing any adverse effects. EGFR and CD44 dual-targeted multifunctional hyaluronic acid nanogels have appeared as a safe and efficacious platform for cancer protein therapy.
- | Clinical, Journal, PD(L)-1 Biomarker, IO biomarker: T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor-infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient. (Pubmed Central) - Oct 31, 2018
The patient has so far remained recurrence-free for 36 months, and several CD8 T cell clones that expanded after treatment were maintained at elevated levels for at least 8 months. Our data show that even in a nonagenarian individual with oligoclonal expansion of CD8 T cells, we can identify activation of tumor-infiltrating CD8 T cell clones in peripheral blood following anti-PD-1-based immunotherapies.
- | Journal: Human CD26high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence. (Pubmed Central) - Sep 23, 2018
These properties license CD26high T cells with a natural capacity to traffic to, regress and survive in solid tumors. Collectively, these findings identify CD4+ T cell subsets with properties critical for improving cancer immunotherapy.