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  • Ali, ArwaUppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi (författare)

Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • Frontiers Media SA,2023
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-511800
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-511800URI
  • https://doi.org/10.3389/fimmu.2023.1146413DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • As an immune adjuvant, proinflammatory allogeneic dendritic cells (AlloDCs) have demonstrated promising immune-priming effects in several preclinical and clinical studies. The effector cells, including NK cells and T cells are widely acknowledged as pivotal factors in the effectiveness of cancer immunotherapy due to their ability to selectively identify and eradicate malignant cells. 4-1BB, as a costimulatory receptor, plays a significant role in the stimulation of effector cell activation. This study evaluated the anti-tumor effects when combining intratumoral administration of the immune-adjuvant AlloDCs with systemic a4-1BB treatment directly acting on effector cells. In both the CT-26 murine colon carcinoma model and B16 murine melanoma model, AlloDCs demonstrated a significant enhancement in the therapeutic efficacy of a4-1BB antibody. This enhancement was observed through the delayed growth of tumors and prolonged survival. Analysis of the tumor microenvironment (TME) in the combined-treatment group revealed an immune-inflamed TME characterized by increased infiltration of activated endogenous DCs and IFN?(+) CD8(+) T cells, showing reduced signs of exhaustion. Furthermore, there was an augmented presence of tissue-resident memory (T-RM) CD8(+) T cells (CD103(+)CD49a(+)CD69(+)). The combination treatment also led to increased infiltration of CD39(+)CD103(+) tumor-specific CD8(+) T cells and neoantigen-specific T cells into the tumor. Additionally, the combined treatment resulted in a less immunosuppressive TME, indicated by decreased infiltration of myeloid-derived suppressor cells and Tregs. These findings suggest that the combination of intratumoral AlloDCs administration with systemic agonistic a4-1BB treatment can generate a synergistic anti-tumor response, thereby warranting further investigation through clinical studies.

Ämnesord och genrebeteckningar

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

  • Gao, MenghanUppsala universitet,Institutionen för cell- och molekylärbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)menga341 (författare)
  • Iskantar, AlexandrosUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (författare)
  • Wang, HaiChinese Acad Sci, CAS Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing, Peoples R China.;Univ Chinese Acad Sci, Beijing, Peoples R China. (författare)
  • Karlsson-Parra, AlexMendus AB, Stockholm, Sweden. (författare)
  • Yu, Di,1985-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)diayu422 (författare)
  • Jin, Chuan,1986-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)chuji162 (författare)
  • Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Frontiers in Immunology: Frontiers Media SA141664-3224

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