Publications by authors named "Maria Vila de Mucha"
Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known.
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- - T-bet is a key transcription factor for CD4 T 1 cells and is also present in other CD4 T cell types, but its role in their differentiation and function is not fully understood.
- - To investigate T-bet expression, researchers tracked its presence using a special mouse model, revealing a unique subset of CD4 T cells that show naïve cell features while being distinct from traditional naïve and memory T cells.
- - These T-bet-experienced cells are inclined to develop into T 1 cells, produce a specific cytokine called IFN-γ upon activation, and are less likely to change into other T cell types, indicating that lineage factors can influence T cell responses even without standard activation markers.
Article Synopsis
- - Tumour mutational burden (TMB) can predict how well patients with non-small cell lung cancer (NSCLC) will respond to immunotherapy, but persistent exposure to antigens can harm T cell function.
- - Research found that higher TMB led to changes in T cell differentiation in untreated NSCLC, such as fewer progenitor-like CD4 T cells and more dysfunctional CD8 and CD4 T cells that resemble those activated by neoantigens.
- - A gene signature indicating the shift from healthy to dysfunctional T cell states was linked to poorer survival rates, highlighting the need for new therapeutic strategies to improve outcomes in NSCLC patients.
In addition to helper and regulatory potential, CD4 T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4 T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4, and this was prevented by interleukin-2 (IL-2) neutralization.
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