ACAP1 Deficiency Predicts Inferior Immunotherapy Response in Solid Tumors.

Area of Science:

• Immunology
• Molecular Biology
• Cancer Research

Background:

• Lymphocyte function relies on endocytic recycling, a process involving ACAP1.
• The expression and role of ACAP1 in lymphocytes remain largely unexplored.

Purpose of the Study:

• To comprehensively analyze ACAP1 expression, regulation, and functional significance in lymphocytes and cancer.

Main Methods:

• Utilized large-scale genomic data (RNA-seq, single-cell sequencing) and immunotherapy cohorts.
• Employed bioinformatics (GSEA, immune cell infiltration algorithms) and experimental validation (Western blot, qPCR, ChIP-PCR, T-cell killing assays).

Main Results:

• ACAP1 is highly expressed in immune cells, particularly in tumor-infiltrating lymphocytes (TILs).
• ACAP1 expression is regulated by DNA methylation and positively influenced by SPI1 binding.
• Elevated ACAP1 correlates with increased TILs (especially CD8+ T cells) and predicts better response to immune checkpoint blockade therapy (ICT).
• ACAP1 depletion impairs T-cell mediated tumor cell killing.

Conclusions:

• ACAP1 is vital for TIL function and anti-tumor immunity.
• ACAP1 deficiency is linked to an immunologically "cold" tumor phenotype and resistance to ICT.