KIAA1429 inhibits colorectal cancer tumor immunity by regulating PD-L1 and CD8+ T cell

Objective This study aims to investigate the effect of the N6-methyladenosine (m6A) methyltransferase KIAA1429 on programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration in colorectal cancer (CRC). Methods The effects of KIAA1429 expression on PD-L1 expression and CD8+T cell infiltration in CRC were analyzed using online databases. Tissue samples from tumor and adjacent normal regions were collected from patients with pathologically confirmed CRC treated at the Affiliated Taizhou People's Hospital of Nanjing Medical University, admitted and diagnosed between 2020 and 2022. Immunohistochemical (IHC) staining was performed to evaluate and compare the expression levels of KIAA1429 and PD-L1, as well as the degree of CD8+ T cell infiltration. In CRC cell lines, quantitative polymerase chain reaction (qPCR) and western blotting were used to measure PD-L1 mRNA and protein expression levels after KIAA1429 knockdown, respectively. After KIAA1429 knockdown in CRC syngeneic mouse models, tumor size and body weight were recorded every 3 days, and flow cytometry was used to assess changes in CD8+ T cell infiltration degree within the tumor tissue. Results Bioinformatics analysis indicated that KIAA1429 was highly expressed in CRC (P<0.05), associa-ted with poor prognosis (P=0.028), and negatively correlated with CD8+T cell infiltration degree (P=3.981×10-2). IHC results demonstrated that KIAA1429 expression levels in CRC were significantly higher than in adjacent normal tissues (P=2.196×10-7), positively correlated with PD-L1 expression levels (P=1.017×10-7), and negatively correlated with CD8+T cell infiltration degree (P=0.021). KIAA1429 knockdown in CRC cells downregulated both PD-L1 mRNA and protein expression levels (P<0.01). In the CRC syngeneic mouse models, KIAA1429 knockdown inhibited tumor growth (P<0.01) and enhanced CD8+T cell infiltration degree (P<0.05). Conclusions The m6A methyltransferase KIAA1429 may suppress tumor immunity in CRC by upregulating PD-L1 expression and reducing CD8+T cell infiltration. Targeting KIAA1429 may help improve the prognosis of CRC patients and enhance the efficacy of CRC immunotherapy.