Tumor occurrence and growth are highly correlated with the degree of inflammation and immunological activity. Reducing the level of inflammation in tumor-bearing body to relieve immune suppression and enhance anti-tumor immune function has become an important strategy for tumor treatment.
To investigate the effect of albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide (SSP) on inhibiting inflammation, reducing immunosuppression, enhancing anti-tumor immune function and slowing the progression of tumor in tumor-bearing rats, and to provide certain scientific basis for the clinical application of combined drugs in tumor.
The rats were put into three groups at random: normal control, model group, and drug treatment group. After the end of drug intervention, the tumor was taken out and weighed to observe the tumor growth of the rats. Tumor necrosis factor (TNF-α), interleukin (IL) 1β, IL-10, perforin, and granzyme B were found by Western blot in the local tumor tissues of experimental rats. The protein expression levels of Arginase-1 (Arg-1) and Cyclooxygenase 2 (COX-2) were determined. HE staining was used to observe the inflammatory infiltration of the tumor. Using flow cytometry, the proportions of anti-tumor immune cells-CD8 + T cells, NK cells, and immunosuppressive cells-in local tumor tissues were evaluated. In addition, spleen T cells isolated from normal rats were co-cultured with spleen myeloid derived suppressor cells (MDSC) from tumor-bearing rats in the model group and the combined treatment group. Cell Trace Far Red was used to identify T cell proliferation, flow cytometry was used to determine the level of T cell activation from CD25 expression, and in vivo immunosuppression in tumor-bearing rats was examined.
The combined therapy group experienced a considerable decrease in tumor weight as compared to the model group. TNF-α and IL-1p levels in the vicinity of the tumor tissues reduced following intervention, although IL-10 levels, which are anti-inflammatory cytokines, did not significantly change. The results of the HE staining revealed that the intervention group's tumor had less inflammatory infiltration than the model group did. After intervention, the percentages of CD8 + T cells and NK cells in local tumor tissues increased. Additionally, the intervention group's levels of protein expression for perforin and granzyme B were considerably higher than those of the model group. In the nearby tumor tissues, there were lots of MDSC. Following the intervention, the proportion of MDSC in the local tumor tissues was significantly reduced, and the expansion of MDSC was reduced. Additionally, the intervention group's COX-2 and Arg-1 protein expression levels in the tumor-specific tissues were significantly lower than those of the model group. The outcomes of in vitro co-culture demonstrated that rats in the combination group had higher levels of T cell proliferation and activation than animals in the model group.
Albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide can reduce the local inflammation level, promote the proportion of CDB + T cells and NK cells and cell killing function, reduce the proportion of MDSC and immunosuppressive level, enhance the anti-tumor immune function of tumor-bearing mice, and slow the growth of tumors.
© 2025. The Author(s).

SL/Kh mice develop a high frequency of retrovirally-induced pre-B lymphomas at 3-6 months of age. They also exhibit an abnormal transient expansion of pre-B cells in the bone marrow, although the relevance of this expansion for lymphomagenesis has remained unclear. Here, we use a dual approach that combines pathology with flow cytometry to more fully characterize the nature and origin of SL/Kh lymphomas. Unexpectedly, our studies showed that SL/Kh lymphomas arise from a rare population of pro/pre-B cells in the thymus. We also identified a 10-fold reduction in Notch1 expression in SL/Kh thymic T cells that is associated with a block in early T cell development, a reduction in the number of thymic T cells with age, and an expansion of thymic pro/pre-B cells. This phenotype is consistent with previous studies showing that Notch1 signaling is essential for lymphoid progenitors to undergo T cell commitment and for suppressing B cell development in the thymus. We propose that this developmental defect provides a niche for early B cells to accumulate in the thymus, which, when combined with subsequent retroviral insertional mutagenesis, results in the induction of pre-B lymphomas that originate in the thymus. This is also consistent with our analysis of the genes insertionally mutated in SL/Kh lymphomas, which shows that many function in signaling pathways such as JAK/STAT and RAS/MAPK/ERK that are commonly deregulated in B-cell lymphomas. Primary human mediastinal large B-cell lymphoma (MLBCL) is another lymphoma that is derived from thymic B cells, although virtually nothing is known about the cause of this rare disease. Our studies provide new insights into an underappreciated class of B-cell lymphomas and a mouse model for the study of MLBCL.

SARS-CoV-2 (Betacoronavirus pandemicum) is responsible for the disease identified by the World Health Organization (WHO) as COVID-19. We designed "CHIVAX 2.1", a multi-epitope vaccine, containing ten immunogenic peptides with conserved B-cell and T-cell epitopes in the receceptor binding domain (RBD) sequences of different SARS-CoV-2 variants of concern (VoCs). We evaluated the immune response of mice immunized with 20 or 60 µg of the chimeric protein with two different alum adjuvants (Alhydrogel® and Adju-Phos®), plus PHAD®, in a two-immunization regimen (0 and 21 days). Serum samples were collected on days 0, 21, 31, and 72 post first immunization, with antibody titers determined by indirect ELISA, while lymphoproliferation assays and cytokine production were evaluated by flow cytometry. The presence of neutralizing antibodies was assessed by surrogate neutralization assays. Higher titers of total IgG, IgG1, and IgG2a antibodies, as well as increased proliferation rates of specific CD4+ and CD8+ T cells, were observed in mice immunized with 60 μg of protein plus Adju-Phos®/PHAD®. This formulation also generated the highest levels of TNF-α and IFN-γ, in addition to the presence of neutralizing antibodies against Delta and Omicron VoC. These findings indicate the potential of this chimeric multi-epitope vaccine with combined adjuvants as a promising platform against viral infections, eliciting a TH1 or TH1:TH2 balanced cell response.

The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research.
© 2024. The Author(s).

Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8 + T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive.
Eight-week-old male wildtype (CD8 +/+ ) and Cd8a knockout (CD8 -/- ) mice were used in a calcium chloride 2 (CaCl 2 )-induced experimental AAA model. At 6 weeks after surgery, CD8 + T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1β, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91 phox ], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8 + T cells of IFN-γ +/+ mice diminished CD8 -/- -mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells.
The vasculoprotective effects of CD8 + T-cell deletion in a mouse CaCl 2 -induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8 + T-cell-derived IFN-γ secretion.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.