Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.

Allergen Immunotherapy: Current and Future Trends

Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.

Applications and Immunological Effects of Quantum Dots on Respiratory System

Quantum dots (QDs), are one kind of nanoscale semiconductor crystals with specific electronic and optical properties, offering near-infrared mission and chemically active surfaces. Increasing interest for QDs exists in developing theranostics platforms for bioapplications such as imaging, drug delivery and therapy. Here we summarized QDs’ biomedical applications, toxicity, and immunological effects on the respiratory system. Bioapplications of QDs in lung include biomedical imaging, drug delivery, bio-sensing or diagnosis and therapy. Generically, toxic effects of nanoparticles are related to the generation of oxidative stresses with subsequent DNA damage and decreased lung cells viability in vitro and in vivo because of release of toxic metal ions or the features of QDs like its surface charge. Lastly, pulmonary immunological effects of QDs mainly include proinflammatory cytokines release and recruiting innate leukocytes or adaptive T cells.

Potential of dietary supplementation with berries to enhance immunity in humans

One of the most prominent concerns that has arisen from global events such as the Coronavirus Disease 2019 (COVID-19) pandemic is how the immune system might be enhanced to provide greater protection against malignant conditions and diseases. Dietary modification is one of the major fields of research, with special focus on how diet interacts with immunity through impacts on factors such as the gut microbiome, inflammation, and nutritional imbalance. This review focuses on current research regarding the use of bioactives derived from berries as a dietary supplement to improve immunity, with discussions of relevant clinical studies. Major bioactive, metabolic compounds of focus- flavonoids, anthocyanins, alkaloids, dietary fiber, and stilbenes- have demonstrated biochemical merits in modulating immunity. In addition, blueberries, goji berries, black raspberries, and cranberries, which have been extensively researched and recently gained interest for their effects on the immune system in animal and cell models, may also hold promise in providing similar benefits to humans, though the precise immunological effects have yet to be clearly determined. Overall, the field of berry research as it relates to diet and immunity shows potential, but more clinical studies will be necessary for a full understanding of the mechanisms of berry immunomodulation.

Application of imprint cytology in assessment of immunological effects of isolated and combined action of selenium and copper nanoparticles

Introduction. Touch Imprint Cytology as the method of impression cytology of smears-prints is of great diagnostic value not only in clinical practice but is also of interest as an express method for assessing the immunological effects of the influence of metal-containing nanoparticles on the tissues of laboratory animals in an experiment. Materials and methods. The study involved the spleen and mesenteric lymph nodes (MLN) of outbred male rats (24 individuals), with an initial weight of 220-230 g, after subchronic intoxication, which was caused by repeated intraperitoneal injections of metal-containing nanoparticles of selenium (SeO) and copper (CuO) nanoparticles (NPs) at a dose of 0.5 mg/kg and their combination three times a week (a total of 18 injections). After sacrificing the rats by decapitation, the spleen and MLN were removed from the animals from each group; made smears were dried at room temperature. Stained according to Leishman. Cell composition and cytological signs were assessed in a light binocular microscope by Carl Zeiss Primo Star with a USCMOS video imaging system at a magnification of 100x and 1000x under cytological criteria. Cell counting in the analysis of spleen and MLN preparations was carried out in percentage - 100 cells from each smear (48 studies), as well as calculating the number of cellular elements per 1 mm2 of the smear surface area, by calculating the absolute amount of each cellular element in the microscope field of view of 0.03 mm2, followed by recalculation per 1 mm2 (the number of studies is 48). Differences between the mean group quantitative results were processed using Student’s criteria using Excel software. Differences between mean values were considered statistically significant if the probability of a random difference did not exceed 5% (p < 0.05). Results. The main results obtained in the study of cytomorphological parameters of smears - spleen prints and MLN of rats after exposure to SeO and CuO NPs, both independently and their combination using two methods for calculating the cellular composition of preparations, are presented. The main changes in the cellular composition during immunological effects are highlighted. Inflammatory reactions of the hyperergic type were revealed when exposed to selenium nanoparticles, both in autonomous action and in combination with copper nanoparticles. The formation of local cellular immunity was noted due to an increase in the level of plasma cells in smears imprints when exposed to copper nanoparticles. Conclusion. Using the impression method of smears-prints in conjunction with the histological examination of tissue preparations allows iimplementing complete cytomorphological parameters in studying the immunological effects of metal-containing nanoparticles.

The Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles

Vaccination is one of the most efficacious and cost-effective ways to protect people from infectious diseases and potentially cancer. The shift in vaccine design from disrupted whole pathogens to subunit antigens has brought attention on to vaccine delivery materials. For the last two decades, nanotechnology-based vaccines have attracted considerable attention as delivery vehicles and adjuvants to enhance immunogenicity, exemplified with the current COVID vaccines. The nanoparticle vaccines display unique features in protecting antigens from degradation, controlled antigen release and longer persisting immune response. Due to their size, shape and surface charge, they can be outstanding adjuvants to achieve various immunological effects. With the safety and biodegradable benefit of calcium phosphate nanoparticles (CaP NPs), they are an efficient carrier for vaccine design and adjuvants. Several research groups have studied CaP NPs in the field of vaccination with great advances. Although there are several reports on the overview of CaP NPs, they are limited to the application in biomedicine, drug delivery, bone regeneration and the methodologies of CaP NPs synthesis. Hence, we summarised the basic properties of CaP NPs and the recent vaccine development of CaP NPs in this review.

Therapeutic Associations Comprising Anti-PD-1/PD-L1 in Breast Cancer: Clinical Challenges and Perspectives

Despite a few cases of long-responder patients, immunotherapy with anti-PD-(L)1 has so far proved rather disappointing in monotherapy in metastatic breast cancer, prompting the use of synergistic therapeutic combinations incorporating immunotherapy by immune-checkpoint inhibitors. In addition, a better understanding of both the mechanisms of sensitivity and resistance to immunotherapy, as well as the immunological effects of the usual treatments for breast cancer, make it possible to rationally consider this type of therapeutic combination. For several years, certain treatments, commonly used to treat patients with breast cancer, have shown that in addition to their direct cytotoxic effects, they may have an impact on the tumor immune microenvironment, by increasing the antigenicity and/or immunogenicity of a “cold” tumor, targeting the immunosuppressive microenvironment or counteracting the immune-exclusion profile. This review focuses on preclinical immunologic synergic mechanisms of various standard therapeutic approaches with anti-PD-(L)1, and discusses the potential clinical use of anti-PD-1/L1 combinations in metastatic or early breast cancer.