NIH3T3 Directs Memory-Fated CTL Programming and Represses High Expression of PD-1 on Antitumor CTLs

Yingyu Qin, Yuna Lee, Jaeho Seo, Taehyun Kim, Jung Hoon Shin, Se-Ho Park

Research output: Contribution to journalArticle

Abstract

Memory CD8+ T cells have long been considered a promising population for adoptive cell therapy (ACT) due to their long-term persistence and robust re-stimulatory response. NIH3T3 is an immortalized mouse embryonic fibroblast cell line. We report that NIH3T3-conditioned medium (CM) can augment effector functions of CTLs following antigen priming and confer phenotypic and transcriptional properties of central memory cells. After NIH3T3-CM-educated CTLs were infused into naïve mice, they predominantly developed to central memory cells. A large number of NIH3T3-CM-educated CTLs with high functionality persisted and infiltrated to tumor mass. In addition, NIH3T3-CM inhibited CTLs expression of PD-1 in vitro and repressed their high expression of PD-1 in tumor microenvironment after adoptive transfer. Consequently, established tumor models showed that infusion of NIH3T3-CM-educated CTLs dramatically improved CTL mediated-antitumor immunity. Furthermore, NIH3T3-CM also promoted human CD8+ T cells differentiation into memory cells. These results suggest that NIH3T3-CM-programmed CTLs are good candidates for adoptive transfer in tumor therapy.

Original languageEnglish
Number of pages1
JournalFrontiers in immunology
Volume10
DOIs
Publication statusPublished - 2019 Jan 1

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Conditioned Culture Medium
Adoptive Transfer
T-Lymphocytes
Neoplasms
Tumor Microenvironment
Cell- and Tissue-Based Therapy
Cell Differentiation
Immunity
Fibroblasts
Antigens
Cell Line
Population

Keywords

  • adoptive cell therapy
  • cytotoxic T lymphocytes
  • memory CD8+ T cells
  • memory precursor
  • NIH3T3-CM

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

NIH3T3 Directs Memory-Fated CTL Programming and Represses High Expression of PD-1 on Antitumor CTLs. / Qin, Yingyu; Lee, Yuna; Seo, Jaeho; Kim, Taehyun; Shin, Jung Hoon; Park, Se-Ho.

In: Frontiers in immunology, Vol. 10, 01.01.2019.

Research output: Contribution to journalArticle

Qin, Yingyu ; Lee, Yuna ; Seo, Jaeho ; Kim, Taehyun ; Shin, Jung Hoon ; Park, Se-Ho. / NIH3T3 Directs Memory-Fated CTL Programming and Represses High Expression of PD-1 on Antitumor CTLs. In: Frontiers in immunology. 2019 ; Vol. 10.
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