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  • Sah, Vasu R.Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Gothenburg, Sweden. (författare)

Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • American Association For Cancer Research (AACR),2023
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-512777
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-512777URI
  • https://doi.org/10.1158/2767-9764.CRC-22-0490DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:237377898URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Jespersen, HenrikUniv Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Oncol,Sahlgrenska Acad, Gothenburg, Sweden.;Oslo Univ Hosp, Dept Oncol, Oslo, Norway. (författare)
  • Karlsson, JoakimUniv Western Australia, Harry Perkins Inst Med Res, Perth, WA, Australia. (författare)
  • Nilsson, Lisa M.Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA, Australia. (författare)
  • Bergqvist, MattiasBiovica Int AB, Uppsala Sci Pk, Uppsala, Sweden. (författare)
  • Johansson, IvaSahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. (författare)
  • Carneiro, AnaSkane Univ Hosp, Dept Oncol, Lund, Sweden. (författare)
  • Helgadottir, HildurKarolinska Institutet,Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. (författare)
  • Levin, MaxUniv Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Oncol,Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. (författare)
  • Ullenhag, GustavUppsala universitet,Cancerimmunterapi(Swepub:uu)gustulle (författare)
  • Stahlberg, AndersUniv Gothenburg, Wallenberg Ctr Mol & Translat Med, Dept Lab Med, Gothenburg, Sweden.;Univ Gothenburg, Inst Biomed, Sahlgrenska Ctr Canc Res, Dept Clin Genet & Genom, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden. (författare)
  • Bagge, Roger OlofssonUniv Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden.;Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden. (författare)
  • Nilsson, Jonas A.Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Gothenburg, Sweden. (författare)
  • Ny, LarsUniv Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Oncol,Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. (författare)
  • Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Gothenburg, Sweden.Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Oncol,Sahlgrenska Acad, Gothenburg, Sweden.;Oslo Univ Hosp, Dept Oncol, Oslo, Norway. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Cancer Research Communications: American Association For Cancer Research (AACR)3:5, s. 884-8952767-9764

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