免疫检查点抑制剂（ICIs）显著改变了癌症治疗领域。大量结直肠癌患者对ICIs治疗表现出不良的响应率。N6-甲基腺苷（m6A）与癌症的发生和发展密切相关。为探索甲基转移酶类似物16（METTL16）在结直肠癌治疗中的作用，我们收集了临床样本和不同的结直肠癌细胞系。通过qPCR和免疫组织化学（IHC）确定了METTL16和PD-L1的表达。在结直肠癌细胞中进行了METTL16的异位表达。使用结直肠癌细胞和T细胞建立了共培养系统以测量免疫逃避。分别通过CCK-8、克隆形成、流式细胞术、Transwell和划痕愈合实验检测细胞存活率、凋亡、迁移和侵袭。通过甲基化RIP（MeRIP）和RNA稳定性实验研究了METTL16对PD-L1的N6-甲基腺苷（m6A）修饰。建立了体内移植模型以测量METTL16对结直肠癌生长的影响。在结直肠癌组织和细胞系中，METTL16下调而PD-L1上调。METTL16增强了细胞增殖、迁移和侵袭，并促进了结直肠癌的体内肿瘤生长。METTL16通过诱导m6A修饰并降低METTL16 RNA的稳定性，从而抑制了METTL16的水平。在结直肠癌细胞中过表达METTL16导致PD-1阳性T细胞比例降低。METTL16的过表达和PD-1的抑制协同抑制了体内结直肠癌细胞的生长。我们的研究确定了METTL16/PD-L1/PD-1调控轴在结直肠癌发展和免疫逃逸中的作用，这为结直肠癌治疗提供了有前景的靶点。

The immune checkpoint inhibitors (ICIs) has dramatically changed the therapeutic area of cancers. A great number of patients with CRC exhibit poor response rate to ICI treatment. N6-methyl adenosine (m6A) is closely correlated with the initiation and progression of cancers. To explore the role of methyltransferase-like 16 (METTL16) in CRC treatment.Clinical samples and different CRC cell lines were collected. The expression of METTL16 and PD-L1 was determined by qPCR, IHC. Ectopic expression of METTL16 was performed in CRC cells. A co-culture system was established using CRC cells and T cells to measure the immune evasion. Cell viability, apoptosis, migration, and invasion were examined by CCK-8, colony formation, flow cytometry, Transwell, and wound healing assay, respectively. The N6-methyl adenosine (m6A) modification of PD-L1 by METTL16 was investigated by methylated RIP (MeRIP) and RNA stability experiment. In vivo xenograft model was established to measure the effects of METTL16 on CRC growth.METTL16 was decreased and PD-L1 was increased in CRC tissues and cell lines. METTL16 enhanced cell proliferation, migration, and invasion, and promoted CRC tumor growth in vivo. METTL16 induced m6A modification and decreased the stability of METTL16 RNA, leading to the suppression of METTL16 level. METTL16 overexpression in CRC cells induced decreased portion of PD-1 positive T cells. Overexpression of METTL16 and inhibition of PD-1 synergistically suppressed in vivo growth of CRC cells.Our work identified the METTL16/PD-L1/PD-1 regulatory axis in CRC development and immune evasion, which represented a promising target for CRC treatment.