Dysregulated Th1 cells in lung squamous cell carcinoma

Area of Science:

• Immunology
• Oncology

Background:

• Lung squamous cell carcinoma (LUSC) is a prevalent lung cancer subtype.
• Th1 cells are crucial for antitumor immunity, supporting CD8+ T cell activity.
• Limited research exists on Th1 cell roles in LUSC.

Purpose of the Study:

• To investigate the function and characteristics of Th1 cells in LUSC.
• To explore the relationship between Th1 cells, CD8+ T cells, and IFN-γ in LUSC.
• To identify molecular mechanisms underlying Th1 cell dysfunction in LUSC.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of T cells from LUSC tissues.
• Multiplex immunofluorescence staining and immunohistochemistry for cell validation.
• Flow cytometry to assess IFN-γ secretion in a simulated tumor microenvironment.

Main Results:

• scRNA-seq revealed IFN-γ+ Th1 cells constitute 25.28% of Th1 cells.
• Decreased IFN-γ in Th1 cells is linked to endoplasmic reticulum (ER) stress.
• A positive correlation was observed between specific Th1 cells (IFN-γ+ STAT1+ T-bet+) and CD8+ T cells.
• Flow cytometry confirmed reduced IFN-γ secretion by Th1 cells in LUSC.

Conclusions:

• Th1 cell function is suppressed in LUSC, potentially linked to ER stress.
• Reduced Th1 cell activity may impair antitumor immunity in LUSC.
• These findings suggest novel therapeutic strategies targeting Th1 cell function in LUSC.