AURKA Enhances Antitumor Immunity by Activating CD4+ T Cell Proliferation in Colorectal Cancer

Colorectal cancer (CRC) ranks third globally in cancer incidence. Aurora Kinase A (AURKA) critically regulates tumor proliferation and microenvironment, yet its dual CRC roles remain unclear.

We integrated bulk RNA-seq, scRNA-seq, and 10x Visium spatial transcriptomics to profile AURKA. Immune infiltration was assessed via CIBERSORT/ssGSEA. Clinical validation used IHC/HE staining. Immunotherapy associations were tested in ICB cohorts and murine models.

Pan-cancer analysis showed CRC-specific AURKA prognostic value (p < 0.05). High AURKA correlated with prolonged OS (median 68 vs 42 months; log-rank P = 0.034), conventional adenocarcinoma (p < 0.001), left-sided tumors (p < 0.001), and absent perineural invasion (p = 0.041). Pathway analyses linked AURKA to cell cycle (G2/M checkpoint) and immune pathways (IL-2/STAT5). Spatial transcriptomics identified peritumoral niches (clusters 6/7/12) co-expressing AURKA, CD4, MKI67, and immune-activation markers (HLA-DRB1, CXCL10). IHC confirmed AURKA-CD4 + T-cell correlation (R = 0.66, p < 0.05). scRNA-seq revealed AURKA dominance in proliferating T cells. High AURKA predicted anti-PD-1 response (HR = 0.44, p = 0.003) and CD4+ memory T-cell expansion in murine models.

AURKA dually regulates tumor proliferation and immune engagement. Its spatial enrichment in T-cell niches supports its use as an immunotherapy biomarker.