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  • Ferencz, BenceNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest (author)

Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms

  • Article/chapterEnglish2024

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  • 2024

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  • LIBRIS-ID:oai:lup.lub.lu.se:ac7b8ec0-b30c-4481-beeb-1db186ad9dd2
  • https://lup.lub.lu.se/record/ac7b8ec0-b30c-4481-beeb-1db186ad9dd2URI
  • https://doi.org/10.1007/s00262-024-03704-7DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Background: Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs. Methods: The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored. Results: Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively). Conclusions: LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.

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  • Török, KláraNational Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest (author)
  • Pipek, OrsolyaEötvös Loránd University (author)
  • Fillinger, JánosNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Csende, KristófNational Institute of Oncology, Budapest (author)
  • Lantos, AndrásNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Černeková, RadoslavaUniversity Hospital Ostrava (author)
  • Mitták, MarcelUniversity Hospital Ostrava (author)
  • Škarda, JozefUniversity Hospital Ostrava,Palacký University (author)
  • Delongová, PatricieUniversity Hospital Ostrava (author)
  • Megyesfalvi, EvelynNational Institute of Oncology, Budapest (author)
  • Schelch, KarinMedical University of Vienna (author)
  • Lang, ChristianMedical University of Vienna (author)
  • Solta, AnnaMedical University of Vienna (author)
  • Boettiger, KristiinaMedical University of Vienna (author)
  • Brcic, LukaMedical University of Graz (author)
  • Lindenmann, JörgMedical University of Graz (author)
  • Rényi-Vámos, FerencNational Institute of Oncology, Budapest,National Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Aigner, ClemensMedical University of Vienna (author)
  • Berta, JuditNational Korányi Institute for Tuberculosis and Pulmonology, Hungary (author)
  • Megyesfalvi, ZsoltMedical University of Vienna,National Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest (author)
  • Döme, BalázsLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,National Korányi Institute for Tuberculosis and Pulmonology, Hungary,National Institute of Oncology, Budapest,Medical University of Vienna(Swepub:lu)ba1464do (author)
  • National Korányi Institute for Tuberculosis and Pulmonology, HungaryNational Institute of Oncology, Budapest (creator_code:org_t)

Related titles

  • In:Cancer Immunology, Immunotherapy73:60340-7004

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