Transcriptomics

Dataset Information

0

Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy


ABSTRACT: T cell rejuvenation by PD-1/PD-L1 blockade, despite emerging as a highly promising therapy for advanced cancers, is only beneficial for a minority of treated patients. There is evidence that a lack of efficient T cell activation may be responsible for the failure. Here, we demonstrate that IL-21 can be targeted to tumor-reactive T cells by fusion of IL-21 to anti-PD-1 antibody. To our surprise, the fusion protein PD-1Ab21 promoted the generation of TSCM-like CD8+ T cells with enhanced cell proliferation. A transcriptome analysis of isolated TN, activated and PD-1Ab-cultured CD44highCD62Lhigh T cells, IL-2-generated TE/TEM, IL-15-generated TCM as well as PD-1Ab21 and IL-21-generated CD44lowCD62Lhigh T cells provides corroborating evidence that PD-1Ab21 induces conversion of activated CD8+ T cells back to a memory subset that is distinct from TCM cells, but similar to TSCM. PD-1Ab21 treatment showed potent antitumor effects in established tumor-bearing mice accompanied with an increased frequency of TSCM and robust expansion of tumor-specific CD8+ T cells with a memory phenotype, and was superior to a combination of PD-1 blockade and IL-21 infusion. Therefore, we have developed a potential strategy to improve the therapeutic effects of immune checkpoint blockade by simultaneously targeting cytokines to tumor-reactive T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE164093 | GEO | 2021/01/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2021-01-28 | GSE140250 | GEO
2023-06-16 | MSV000092193 | MassIVE
2020-05-01 | GSE145896 | GEO
2013-05-06 | E-MTAB-1569 | biostudies-arrayexpress
2023-06-16 | GSE206325 | GEO
2017-01-06 | GSE93211 | GEO
2021-11-23 | GSE189170 | GEO
2016-06-29 | GSE68003 | GEO
2015-05-12 | E-GEOD-61697 | biostudies-arrayexpress
2016-06-29 | E-GEOD-68003 | biostudies-arrayexpress