Lingyun Ye

Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant’s immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. NCT00553228.