Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.

Background: Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs. Major depressive disorder (MDD) in older adults has been associated with many hallmarks of senescence in whole blood, leukocytes, and plasma, supporting a strong connection between iSCs and MDD. Here, we investigated the prevalence and phenotype of iSCs in older adults with MDD. Using a single-cell phenotypic approach, circulating immune cells were examined for iSC biomarkers and their relationship to depression and inflammation. Results: PBMCs from older adults with MDD (aged 69.75 ± 5.23 years) and healthy controls (aged 71.25 ± 8.8 years) were examined for immune subset distribution and senescence biomarkers (i.e., lack of proliferation, senescence-associated heterochromatin foci (SAHF), and DNA damage). Dual-expression of SAHF and DNA damage was categorized by low, intermediate, and high expression. A significant increase in the number of high expressing total PBMCs (p = 0.01), monocytes (p = 0.008), a trending increase in the number of high expressing CD4 T cells (p = 0.06) was observed overall in those with MDD. There was also a significantly lower proportion of intermediate expressing cells in monocytes and CD4 T cells in MDD (p = 0.01 and p = 0.05, respectively). Correlation analysis revealed associations between iSCs and mRNA expression of factors related to SASP and immune cell function. Conclusion: MDD is associated with increased senescent cell biomarkers in immune cell populations delineated by distinct levels of SAHF and DNA damage. Inflammatory markers might serve as potent indicators of iSC burden in MDD.

Field safety experience with an autologous cancer vaccine in tumor-bearing cats: a retrospective study of 117 cases (2015-2020).

OBJECTIVES: The aim of this study was to determine the frequency and severity of adverse events (AEs) reported from use of an adjuvanted whole-cell autologous cancer vaccine in cats with solid tumors under field conditions. METHODS: The case accession database at Torigen Pharmaceuticals was searched to identify client-owned cats that underwent biopsy or surgical resection of their primary tumor, had histologic confirmation of neoplasia and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. Records were reviewed for any reported AEs. RESULTS: In total, 117 cats met the inclusion criteria and received 422 doses of autologous cancer vaccine. Six (5.1%) cats had seven reported AEs, with the majority of these (85.7%) being characterized as grade 1 or 2 (mild) and resolving without medical intervention. CONCLUSIONS AND RELEVANCE: AEs were infrequent in cats treated with an adjuvanted whole-cell autologous cancer vaccine under typical field use conditions. This form of active cancer immunotherapy appears to be well tolerated by cats and may represent a treatment option for owners who are concerned about AEs associated with chemotherapy or radiotherapy. Additional studies are warranted to determine the efficacy of this form of individualized immunotherapy in cats with solid tumors.

Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study.

BACKGROUND: Canine hemangiosarcoma (HSA) is an aggressive cancer arising from multipotential bone marrow-derived stem cells. Anthracycline chemotherapy drugs have been the mainstay adjuvant chemotherapy following surgery with only modest improvement in survival and an attendant risk for adverse events. Immunotherapy, using a whole cell autologous cancer vaccine adjuvanted with MIM-SIS, may improve outcomes for dogs with HSA with a lower risk for adverse events compared with chemotherapy. RESULTS: In cultured DH82 canine monocyte-like cells, autologous cancer vaccines prepared from 13 dogs with HSA increased MHC-II surface expression ranging from 20.0-60.4% on single-stained cells, CD80 surface expression ranging from 23.7-45.9% on single-stained cells, and MHC-II/CD80 surface expression ranging from 7.2-20.1% on double-stained cells. Autologous cancer vaccines were able to, on average, stimulate an up-regulation of MHC-II and CD80 by 48-fold as compared to media only (MHC-II + CD80 + cells: 12.19 ± 3.70% vs. 0.25 ± 0.06%; p < 0.001). The overall median survival time for dogs treated with the autologous cancer vaccine was 142 days (range, 61 to 373 days). Dogs treated with the autologous cancer vaccine or maximum tolerated dose (MTD) chemotherapy had significantly (P < 0.001) longer survival than dogs treated with surgery alone. The 1-year survival rate was 12.5% for dogs treated with the autologous cancer vaccine, and 0% for dogs treated with surgery alone or MTD chemotherapy. No adverse events were observed in the dogs treated with the autologous cancer vaccine. CONCLUSIONS: The adjuvanted autologous cancer vaccine is capable of up-regulating MHC-II and CD80 in cultured canine monocyte-derived cells, which are important stimulatory molecules in generating an immune response and improves survival time in dogs with metastatic (stage III) HSA when compared to surgical treatment alone. Autologous cancer vaccine-treated dogs had survival similar to those dogs treated with MTD chemotherapy without any observed adverse events. This autologous cancer vaccine represents an effective form of individualized immunotherapy that is an appealing option for dog owners not wanting to pursue adjuvant chemotherapy for HSA.

Distributions of intravenous injected iodine nanoparticles in orthotopic u87 human glioma xenografts over time and tumor therapy.

Aim: To analyze the localization, distribution and effect of iodine nanoparticles (INPs) on radiation therapy (RT) in advanced intracerebral gliomas over time after intravenous injection. Materials & methods: Luciferase/td-tomato expressing U87 human glioma cells were implanted into mice which were injected intravenously with INPs. Mice with gliomas were followed for tumor progression and survival. Immune-stained mouse brain sections were examined and quantified by confocal fluorescence microscopy. Results: INPs injected intravenously 3 days prior to RT, compared with 1 day, showed greater association with CD31-staining structures, accumulated inside tumor cells more, covered more of the tumor cell surface and trended toward increased median survival. Conclusion: INP persistence and redistribution in tumors over time may enable greater RT enhancement and clinically relevant hypo-fractionated-RT and may enhance INP efficacy.