Hepatocyte growth factor restrains tumor-reactive cytotoxic MET+ CD8+ T cell immunity in melanoma
Year: 2026
Type: article
Abstract: The hepatocyte growth factor (HGF)-MET axis is a major oncogenic pathway, yet how it shapes cytotoxic T cell function remains unclear. Here, we show that MET identifies a transcriptionally and functionally distinct subset of tumor-reactive CD8 + T cells, while prior HGF exposure attenuates their effector function. Using Pmel-1 CD8 + T cells and a CD8 + T cell-specific MET-deficient mouse model, RNA sequencing revealed that MET + CTLs were enriched for cytotoxic, interferon, TCR signaling, and inflammatory programs, whereas HGF exposure was associated with immunoregulatory transcriptional changes, including enrichment of the IL-6/JAK/STAT3 signaling gene set, and downregulation of effector genes. Functionally, MET + CTLs displayed enhanced antigen-specific killing and superior tumor control, with increased degranulation and lower inhibitory checkpoint expression. Prior HGF exposure or MET deficiency was associated with reduced effector responses. These findings identify MET as a potential marker of a highly cytotoxic CD8 + T cell state and show that prior HGF exposure can attenuate their effector function, suggesting the HGF-MET axis as a potential modulator of antitumor CD8 + T-cell immunity.
Source: Frontiers in Immunology
Institutions: University of Geneva, University Hospital of Geneva
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225738791