Eomes sustains progenitor CD4⁺ T helper cells to promote anti-tumor immunity during immunotherapy [scRNA]

Here, we show that the transcription factor Eomesodermin (Eomes) is essential for Th–mediated anti-tumor immunity by orchestrating the differentiation and maintenance of an exhausted-like Th cell lineage, which is transcriptionally and functionally distinct from conventional effector or memory Th subsets.

This Eomes-dependent program is further enhanced by 4-1BB stimulation, promoting effective Th cell–mediated tumor control. The precursor subset of this lineage (pTh) expresses stemness-associated transcription factors, displays self-renewal capacity, and can differentiate into effector cells capable of controlling tumor growth. At the transcriptional level, Eomes supports the survival, metabolic fitness, and apoptotic resistance of this lineage.