{
  "abstract": "Background Despite the integration of atezolizumab into first-line chemotherapy regimens, prognosis for patients with extensive-stage small cell lung cancer (ES-SCLC) remains poor, with limited improvement in overall survival (OS). In this context, we investigated the role of dendritic cells (DCs) both as immunotherapeutic agents and as mediators of the immune response triggered by atezolizumab. While our group has previously described the relevance of XCR1 + cDC1s in sustaining T cell function during chronic infection,1 their contribution to cancer immunotherapy remains unclear.Methods This phase 1b/2 trial evaluates autologous tumor lysate-pulsed DC vaccination combined with atezolizumab as maintenance therapy in ES-SCLC. After induction with chemotherapy and atezolizumab, patients received up to six intradermal doses of 10×10 6 mature DCs, along with 1,200 mg of atezolizumab IV every three weeks. Monitoring included analysis of changes in DCs and T cell subsets and ctDNA in blood, as well as tumor tissue profiling through whole exome sequencing (WES), RNA expression (Nanostring nCounter), and immunohistochemistry. We present a comparative analysis of clinical, molecular, and immune cell phenotype changes during treatment, focusing on differences between long-term survivors and non-respondersResults Twenty patients were enrolled; 18 received DC vaccination (median 3 doses, range 1–6). After a median follow-up of 25.7 months, median progression-free survival was 4.7 months (95% CI: 4.2–6.9) and OS was 11.2 months (95% CI: 6.3–17.9). Six patients (33%) achieved survival beyond 24 months, with four (22%) remaining progression-free. No significant differences were observed in long-term survivors regarding clinical features, PD-L1 expression, SCLC molecular subtype, or tumor mutational burden (TMB) ( table 1). Long-term survivors displayed expansion of XCR1+ cDC1s (p=0.03) and CXCR5+PD1+ CD8+ T cells (p=0.05) post-induction (figure 1) and showed higher RNA expression levels of RAF1 (p=0.03), JAK2 (p=0.001), TYK2 (p=0.03), and ZBTB16 (p=0.006) pretreatment. Clonal hematopoiesis of indeterminate potential (CHIP) was found in two of six long-term survivors.Conclusions Induction therapy with chemotherapy plus atezolizumab, followed by maintenance with DC vaccination and atezolizumab, led to long-term survival in a subset of patients with ES-SCLC. This outcome was associated with expansion after treatment of XCR1 + cDC1s and CXCR5+PD1+ CD8+ T cells and a distinct immune transcriptional signature. These findings support further exploration of DC-based strategies to enhance the efficacy of immune checkpoint blockade in SCLC. Final analysis will be conducted using a data cut-off date of June 20th, 2025, and updated results will be presented at the meeting.Acknowledgements Anna Llabres (CRO)Trial Registration NCT04487756Reference Domenjo-Vila E, Casella V, Iwabuchi R, et al. XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections. Cell Rep. Feb 28 2023;42(2):112123. doi:10.1016/j.celrep.2023.112123Ethics Approval Written informed consent was obtained from the patient for inclusion in this study, appoved from ECAbstract 350 Figure 1Overall survival. OS according to CXCR5+ PD1+ CD8+ T cells (TPEX) and XCR1+cDC1Abstract 350 Table 1Patient characteristicsIHC-A: ASCL1 dominant; IHC-A*: ASCL1 only; IHC-TN: ASCL1/NEUROD1 double-negative POU2F3-negative; IHC-P: ASCL1/NEUROD1 double-negative POU2F3-positive; IHC-AN: ASCL1/NEUROD1 double-positive; IHC-N: NEUROD1 dominant; uk: unkown",
  "authors": [
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Maria Gonzalez-Cao"
    },
    {
      "affiliations": [
        "Universitat Pompeu Fabra, Barcelona, Spain"
      ],
      "name": "Marta Sistere-Oro"
    },
    {
      "affiliations": [
        "ICO-Badalona, Hospital Germans Trias i Pujol, Badalona, Spain"
      ],
      "name": "Teresa Moran"
    },
    {
      "affiliations": [
        "Hospital Clinic, Barcelona, Spain"
      ],
      "name": "Noemi Reguart"
    },
    {
      "affiliations": [
        "Universitat Pompeu Fabra, Barcelona, Spain"
      ],
      "name": "Andreas Meyerhans"
    },
    {
      "affiliations": [
        "Hospital Clinic, Barcelona, Spain"
      ],
      "name": "Raquel Cabezon"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Andres Aguilar"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Ruth Roman"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Miguel Angel Molina Vila"
    },
    {
      "affiliations": [
        "Universitat Pompeu Fabra, Barcelona, Spain"
      ],
      "name": "Kürşat Birgin"
    },
    {
      "affiliations": [
        "Universitat Pompeu Fabra, Barcelona, Spain"
      ],
      "name": "Eva Domenjó Vila"
    },
    {
      "affiliations": [
        "Universitat Pompeu Fabra, Barcelona, Spain"
      ],
      "name": "Gemma Piqué"
    },
    {
      "affiliations": [
        "Teknon Hospital, Barcelona, Spain"
      ],
      "name": "Roxana Reyes"
    },
    {
      "affiliations": [
        "Hospital General de Catalunya, Sant Cugat, Barcelona, Spain"
      ],
      "name": "Irene Moya"
    },
    {
      "affiliations": [
        "Hospital Sagrat Cor, Barcelona, Spain"
      ],
      "name": "Lluis Cirera"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Victor Albarran"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Carlos Esparre"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Ana Drozdowskyj"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain, Spain"
      ],
      "name": "Elizabeth Martinez"
    },
    {
      "affiliations": [
        "Dexeus University Hospital, Barcelona, Spain"
      ],
      "name": "Rafael Rosell"
    },
    {
      "affiliations": [
        "Hospital Clinic, Barcelona, Spain",
        "Catalan Institution for Research and Advanced Studies, Barcelona, Spain"
      ],
      "name": "Manel Juan"
    },
    {
      "affiliations": [
        "Hospital Clinic, Barcelona, Spain",
        "Catalan Institution for Research and Advanced Studies, Barcelona, Spain"
      ],
      "name": "Daniel Benitez"
    }
  ],
  "title": "350 Long term survivors from Phase Ib-II trial of tumor-loaded monocyte-derived dendritic cell vaccination plus atezolizumab in ES-SCLC",
  "uid": "b0726505-d762-5334-8dbd-4ed50c0bf7d7"
}