Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors

Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an “in-situ tumor vaccine,” inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.

Missed opportunities to identify cryptococcosis in COVID-19 patients: a case report and literature review

SARS-CoV-2 may activate both innate and adaptive immune responses ultimately leading to a dysregulated immune response prompting the use of immunomodulatory therapy. Although viral pneumonia increases the risk of invasive fungal infections, it remains unclear whether SARS-CoV-2 infection, immunomodulatory therapy, or a combination of both are responsible for the increased recognition of opportunistic infections in COVID-19 patients. Cases of cryptococcosis have previously been reported following treatment with corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors, for patients with autoimmune diseases, but their effect on the immunologic response in patients with COVID-19 remains unknown. Herein, we present the case of a patient with COVID-19 who received high-dose corticosteroids and was later found to have cryptococcosis despite no traditional risk factors. As our case and previous cases of cryptococcosis in patients with COVID-19 demonstrate, clinicians must be suspicious of cryptococcosis in COVID-19 patients who clinically deteriorate following treatment with immunomodulatory therapies.

Antibody response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease – results of a single-center cohort study in a tertiary hospital in Germany

COVID-19 was first described in 2019, with significant impact on everyday life since then. In 2020, the first vaccine against COVID-19 was approved. Little is known about immune response to vaccination in patients with inflammatory bowel disease (IBD). Aim of our study was to investigate antibody response to SARS-CoV-2 vaccination in IBD patients receiving immunomodulators/biologics compared to healthy controls. This was a single-center retrospective study. 72 patients with IBD were included. Data from 72 healthy employees were used as control group matched by propensity score. Blood samples were analyzed for antibody response. 65 (90.3%) patients of the IBD group received immunomodulatory therapy. Mean antibody level for IBD patients was 1257.1 U/ml (SD 1109.626) in males and 1500.1 U/ml (SD 1142.760) in females (reduced antibody response IBD group 1383.76 U/ml SD 1125.617; control group 1885.65 U/ml SD 727.572, p < 0.05)). There was no vaccination failure in IBD group. After first vaccination, side effects were reported more often in IBD patients (total symptoms IBD group 58.3 %, control group 34.5 %, p < 0.007) with the opposite after the second vaccination (total symptoms IBD group 55.4 %, control group 76 %, p = 0.077)). There was a trend to reduced immune response in elderly. Disease duration and immunomodulatory therapy had no impact on immune response. Longer time to last medication given and time passed to vaccination in IBD group seem to have a positive impact on antibody levels. High antibody response to vaccination in all patients with IBD was seen. Vaccination was well tolerated. Concomitant immunomodulatory therapy had no impact on seroconversion. Antibody levels in the IBD group were lower compared to control group.

Central Multifocal Choroiditis: Platelet Granularity as a Potential Marker for Treatment With Steroid-Sparing Immunomodulatory Therapy

PurposeWe aimed to evaluate the blood cell composition in patients with central multifocal choroiditis (cMFC), a rare form of posterior uveitis predominantly affecting young myopic women.MethodsIn this retrospective observational case-control study, a 104-parameter automated hematocytometry was conducted by the Cell-Dyn Sapphire hematology analyzer for 122 cases and 364 age- and sex-matched controls. Cox proportional regression analysis was used to assess the relation between the blood cell composition and the time between disease onset (first visit) and the start of systemic corticosteroid-sparing immunomodulatory therapy (IMT).ResultsAt a false discovery rate of 5% (Padj), we identified a decrease of blood monocytes in cases with cMFC, which could be attributed to disease activity. Cox proportional hazard analysis including age and sex revealed that increased platelet granularity (measured by mean intermediate angle scatter) was an independent risk factor for treatment with IMT (hazard ratio = 2.3 [95% confidence interval = 1.28 - 4.14], Padj = 0.049). The time between the first presentation and the start of IMT was 0.3 years in the group with an increased platelet granularity and 3.4 years in the group without increased platelet granularity.ConclusionsPatients with cMFC demonstrated a decrease in blood monocytes. Moreover, platelet granularity could potentially be used as a marker for treatment with IMT.