The transcription factor Eomes drives a stemness program in CD4+ T cells that promotes anti-tumor immunity in response to immunotherapy
Abstract
T helper (Th) cells contribute to tumor immunity, yet the subsets and differentiation programs involved remain unclear. Here, we show that the transcription factor Eomesodermin (Eomes) is essential for Th-mediated anti-tumor immunity. Eomes orchestrated the differentiation and maintenance of an exhausted-like Th cell lineage, transcriptionally and functionally distinct from conventional effector or memory Th subsets. This Eomes-dependent program was enhanced by 4-1BB stimulation and promoted effective Th-cell-mediated tumor control. The progenitor subset of this lineage (pTh) expressed stemness-associated transcription factors, displayed self-renewal capacity, and seeded effector subsets capable of controlling tumor growth. At the transcriptional level, Eomes supported the survival, metabolic fitness, and apoptotic resistance of this lineage. Eomes⁺ pTh cells exhibited conserved transcriptional features in humans across multiple tumor types. As the most expanded Th cell population upon immune checkpoint inhibitor therapy, targeting these cells has potential to improve current immunotherapies.
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BibTeX
@article{agesta2026transcription,
title = {{The transcription factor Eomes drives a stemness program in CD4+ T cells that promotes anti-tumor immunity in response to immunotherapy}},
author = {Arantxa Agesta and Chloé Ferrand and Anne-Louise Le Dorze and Cindy Peillex and Nadège Carrié and Rebecca Barascud and Arthur Palak and Lucie Esteban and Tanguy Bernal and Emeline Joulia and Céline Colacios and Tania Margarido Pereira and Romain Peroceschi and Andrea Pichler and Adeline Chaubet and Margot Zahm and Abdelhadi Saoudi and Hicham El Costa and Veronique Adoue and Benjamin Lu and Liliana Lucca and Ludovic Martinet and Anne Dejean},
journal = {Immunity},
year = {2026},
month = oct,
doi = {10.1016/j.immuni.2026.05.018},
url = {https://hal.science/hal-05783210v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - The transcription factor Eomes drives a stemness program in CD4+ T cells that promotes anti-tumor immunity in response to immunotherapy
AU - Arantxa Agesta
AU - Chloé Ferrand
AU - Anne-Louise Le Dorze
AU - Cindy Peillex
AU - Nadège Carrié
AU - Rebecca Barascud
AU - Arthur Palak
AU - Lucie Esteban
AU - Tanguy Bernal
AU - Emeline Joulia
AU - Céline Colacios
AU - Tania Margarido Pereira
AU - Romain Peroceschi
AU - Andrea Pichler
AU - Adeline Chaubet
AU - Margot Zahm
AU - Abdelhadi Saoudi
AU - Hicham El Costa
AU - Veronique Adoue
AU - Benjamin Lu
AU - Liliana Lucca
AU - Ludovic Martinet
AU - Anne Dejean
PY - 2026
DA - 2026/10/07
JO - Immunity
DO - 10.1016/j.immuni.2026.05.018
UR - https://hal.science/hal-05783210v1
AB - T helper (Th) cells contribute to tumor immunity, yet the subsets and differentiation programs involved remain unclear. Here, we show that the transcription factor Eomesodermin (Eomes) is essential for Th-mediated anti-tumor immunity. Eomes orchestrated the differentiation and maintenance of an exhausted-like Th cell lineage, transcriptionally and functionally distinct from conventional effector or memory Th subsets. This Eomes-dependent program was enhanced by 4-1BB stimulation and promoted effective Th-cell-mediated tumor control. The progenitor subset of this lineage (pTh) expressed stemness-associated transcription factors, displayed self-renewal capacity, and seeded effector subsets capable of controlling tumor growth. At the transcriptional level, Eomes supported the survival, metabolic fitness, and apoptotic resistance of this lineage. Eomes⁺ pTh cells exhibited conserved transcriptional features in humans across multiple tumor types. As the most expanded Th cell population upon immune checkpoint inhibitor therapy, targeting these cells has potential to improve current immunotherapies.
SN - 1074-7613
ER -