Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A Review of the Literature.

BACKGROUND: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer. OBJECTIVE: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients. RESULTS: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success. CONCLUSION: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.

Clinical characteristics and mortality predictors of patients with cancer hospitalized by COVID-19 in a pediatric third-level referral center.

Background: More than 135 million COVID-19 cases (coronavirus disease 2019) have been reported worldwide until today, with over 2.9 million deaths. Several studies have demonstrated that disease severity is lower in the pediatric population than in adults; however, differences are described in patients with chronic diseases, including oncological patients. Current world literature suggests patients with comorbidities, including cancer, have an increased risk of unfortunate outcomes. Therefore, our objective was to describe the clinical characteristics and epidemiological factors associated with mortality in a cohort of pediatric cancer patients hospitalized for COVID-19. Methods: This is a retrospective, descriptive study of the cases of patients with cancer hospitalized for COVID-19. A total of 40 pediatrics were included in the analysis. Data from pediatric patients with COVID-19 included clinical and epidemiological records, laboratory, imaging studies, COVID-19 diagnostic methods, and medical treatment. Results: Of the 40 pediatric patients admitted with cancer with a confirmed diagnosis of COVID-19, 42.5% were solid tumors, 40% leukemias, and 17.5% lymphomas. The clinical parameters associated with mortality were stage IV tumor (p = 0.029) and intubation (p < 0.001). The biochemical factors associated with lower survival were thrombocytopenia under 25,000 cells/mm3 (p < 0.001), D-dimer over 1 µg/ml (p = 0.003), clinical malnutrition (p = 0.023), and disseminated intravascular coagulation (p = 0.03). Conclusion: Our findings showed that the fever was the most frequent symptom, and the clinical parameters associated with mortality were stage IV tumor, intubation, saturation percentage, RDW, platelets, creatinine, ALT, D-dimer, ferritin, and FiO2 percentage. The thrombocytopenia, D-dimer, nutritional status, and disseminated intravascular coagulation were significantly associated with lower survival.

Exposure to biomass smoke, cigarettes, and alcohol modifies the association between tumour necrosis factor (-308G/A, -238G/A) polymorphisms and tuberculosis in Mexican carriers.

INTRODUCTION: Exposure to biomass smoke, cigarettes, alcohol, and the impairment of immunoregulation are considered to be risk factors for tuberculosis. Tumour necrosis factor (TNF) -308G/A and -238G/A gene polymorphisms have been associated with tuberculosis. However, the results remain inconsistent. The aim of this study was to determine the association between TNF polymorphisms and tuberculosis in the presence of biomass smoke, cigarettes, and alcohol in a Mexican population. MATERIAL AND METHODS: TNF polymorphisms were determined in 118 tuberculosis patients and 223 controls. We performed a univariate, bivariate, stratified analysis. Odds ratios, confidence intervals, and p-values were calculated. RESULTS: Occupational biomass smoke exposure was associated with tuberculosis between the patients and controls (OR = 1.70, 95% CI: 1.08-2.70, p = 0.02). We also found an association of the -308A allele carriers between the patients and controls without exposure to occupational (p = 0.04, OR = 0.16, 95% CI: 0.01-0.92) and in-home (p = 0.02, OR = 0.14, 95% CI: 0.01-0.81) biomass smoke, as well as an association with alcohol (p = 0.01, OR = 0.24, 95% CI: 0.05-0.75). The haplotype analysis revealed an association of the -308A/-238G haplotype between patients and nonconsanguineous controls without exposure to occupational (p = 0.02, OR = 0.12, 95% CI: 0.01-0.99) and in-home (p = 0.01, OR = 0.1, 95% CI: 0.01-0.9) biomass smoke, cigarette use (p = 0.04, OR = 0.28, 95% CI: 0.08-0.98), and alcohol (p = 0.02, OR = 0.22, 95% CI: 0.05-0.88) intake. CONCLUSIONS: The TNF -308A allele and the -308A/-238G haplotype are associated with tuberculosis, as are exposure to biomass smoke, cigarettes, and alcohol. No association for the -238G/A polymorphism was found. Our results provide insight into a possible protective role of TNF polymorphisms in tuberculosis in our population.

Genetic polymorphism of tumor necrosis factor promoter region and susceptibility to develop Hodgkin lymphoma in a Mexican population.

Hodgkin lymphoma (HL) is a rare neoplasm of the lymphatic system, in which inflammation and allelic variants in cytokines have been proposed as etiological factors. Epstein-Barr virus infection is often associated as a risk factor in HL and since cytokines are involved in the humoral response to viral infection. Our aim was to study the association between single nucleotide polymorphisms (SNPs) located in the tumor necrosis factor (TNF) gene (- 376G> A, - 238G> A and 581G> A) in a sample of Mexican patients (56 cases) and their susceptibility to develop HL, comparing these SNPs among healthy individuals (127 controls). Frequencies for TNF - 238G> A and TNF 581G> A showed no significant differences between cases and controls. However, the proportion of cases with the GA genotype of - 376 SNP showed a significant difference as compared to controls, odds ratio = 4.41 (95% confidence interval: 1.21-16.6), p = 0.02. We found that in this group of patients from Mexico the SNP - 376G> A in TNF shows an association with higher risk for HL.