BACKGROUND:Despite the incorporation of atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody, into first-line chemotherapy regimen, survival in patients with extensive-stage small cell lung cancer (ES-SCLC) remains poor. Given the role of dendritic cells (DCs) in modulating responses to anti-programmed cell death protein 1 (PD-1) antibodies, a promising avenue is the development of vaccines based on DCs, together with the evaluation of how DC phenotypic modifications shape treatment efficacy. MATERIALS AND METHODS:This is a single-arm, phase Ib/II, open-label clinical trial investigating the safety and activity of combining autologous tumor lysate pulsed DCs administered intradermally with intravenous atezolizumab as maintenance therapy for patients with ES-SCLC. Following leukapheresis, monocytes were differentiated ex vivo into mature DCs and loaded with irradiated autologous tumor lysate. After standard induction therapy (four cycles of carboplatin, etoposide, and atezolizumab), patients received up to six doses of mature DCs intradermally, along with intravenous atezolizumab 1,200 mg every 3 weeks, until disease progression. RESULTS:20 patients were enrolled, including six patients with brain metastases. 18 patients received DC vaccination, with a median of three doses (range 1-6). Most grade 3-4 treatment-related adverse events were hematological and related to chemotherapy. DC vaccination was well tolerated, with only grade 1-2 transient skin irritation at the injection site. Among 18 evaluable patients, 17 (94.4%) achieved an objective response. After a median follow-up of 31.4 months, progression-free survival at 2 years (PFS2y) was 20% (95% CI 6.4% to 39.1%), median overall survival (OS) 11.2 months (95% CI 6.3 to 26.0) and OS3y 22.5% (95% CI 6.8% to 43.6%). Six patients achieved long survival (median 30.5 months, range 23.4-36.2). Expansion of conventional type DC1 (cDC1s) XCR1+ and stem-like progenitor-exhausted (CXCR5+PD-1+) CD8+ T cells following chemotherapy plus atezolizumab was associated with improved PFS (HR 0.94, 95% CI 0.90 to 0.99 and HR 0.59, 95% CI 0.39 to 0.89). CONCLUSION:DC immunization combined with atezolizumab maintenance following standard chemotherapy plus atezolizumab treatment is well tolerated. Its clinical activity cannot be definitively determined in this study, as it was administered as maintenance therapy; however, the observed rate of long-term survivors suggests a potential benefit. Our findings suggest a pivotal role for cDC1s in mediating the antitumor activity in long-term survivors. TRIAL REGISTRATION NUMBER:NCT04487756.
BACKGROUND:Dyshidrotic eczema (DE), also termed acute and recurrent vesicular dermatitis, is a vesicular clinical pattern of hand eczema (HE) with heterogeneous aetiologies. OBJECTIVES:To characterise the clinical-allergological profile of patients with DE and to compare it with non-DE HE subtypes. METHODS:A multicentre, retrospective, observational study was conducted using data from the Spanish Contact Dermatitis Registry (2019-2024). RESULTS:Of 4378 patients with HE, 559 were diagnosed with DE. A longer median disease duration (24 vs. 14 months) and more frequent palmoplantar involvement (16% vs. 7%) were observed in DE compared with non-DE HE. At least one positive patch test was identified in 43% of DE versus 52% in non-DE HE. Although overall sensitisation patterns were largely comparable, DE showed lower sensitisation rates to 2-HEMA, carba mix and thiuram mix. Occupational factors were less frequently implicated in DE (9% vs. 29%) compared with non-DE HE. CONCLUSIONS:Despite a high overall frequency of contact allergen sensitisation, the pattern of findings suggests that the dyshidrotic phenotype may follow a clinical course less dependent on external or occupational triggers, pointing towards a relatively greater contribution of endogenous factors compared with other HE subtypes.
