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

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

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

Article/chapterEnglish2023

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Frontiers Media SA,2023
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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

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
ilixadencel
allogeneic dendritic cells
& alpha
4-1BB therapy
tissue-resident CD8(+) T-cells
tumor-reactive CD8(+) T-cells
tumor-specific CD8(+) T-cells

Added entries (persons, corporate bodies, meetings, titles ...)

Gao, MenghanUppsala universitet,Institutionen för cell- och molekylärbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)menga341 (author)
Iskantar, AlexandrosUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)
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. (author)
Karlsson-Parra, AlexMendus AB, Stockholm, Sweden. (author)
Yu, Di,1985-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)diayu422 (author)
Jin, Chuan,1986-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)chuji162 (author)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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