PRDM15 通过激活 PVR/TIGIT 轴抑制组织驻留记忆 T 细胞的反应，从而介导胃癌免疫抑制

We found that the T RM cells representing the majority of tumor-infiltrating lymphocytes and expressing high level of immune checkpoint TIGIT in GC tissue. This study aims to elucidate the mechanisms through which GC cells modulate T RM cells by PVR/TIGIT axis to facilitate immune evasion.

The immune status of GC was evaluated by quantifying T cell subsets in GC tissues through flow cytometry. The biological functions and molecular mechanisms by which the oncogenic factor PRDM15 mediates tumor immune evasion were investigated through the PVR/TIGIT axis using transcriptome sequencing, Chromatin immunoprecipitation (ChIP) assay and Co-immunoprecipitation assay. The therapeutic potential of PRDM15/PVR/TIGIT was analyzed using tumor-bearing models.

We confirmed that PRDM15 promotes the transcription of PVR which is the ligand of TIGIT in GC cells. Aberrantly high expression of PRDM15 in GC tissues was associated with higher TNM stages and T cell immunosuppressive state in GC patients. PRDM15 was found to upregulate the proliferation, invasion and migration of GC cells. When co-cultured with T RM cells with high TIGIT expression, PRDM15 activated the PVR/TIGIT axis to inhibit T RM cells activation by upregulating PVR expression in GC cells. Mechanistically, PRDM15 recruited the histone methyltransferase complex PRMT5/Mep50/WDR5 to activate PVR transcription.

This study demonstrated that PRDM15 in GC cells could recruits the histone methyltransferase complex PRMT5/Mep50/WDR5 to promote PVR transcription, thereby activating the PVR/TIGIT axis, which inhibits T RM cells activation and mediates immune escape and GC progression.