Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response and cancer prognosis. Although many explorations have revealed that high TMB may yield many neoantigens to incite antitumor immune response, a systematic exploration of the correlation between TMB and immune signatures in different cancer types is lacking. We classified cancer into the lower-TMB subtype and the higher-TMB subtype for each of 32 cancer types based on their somatic mutation data from the Cancer Genome Atlas (TCGA), and compared the expression levels of immune-related genes and gene-sets between both subtypes of cancers in each cancer type. In some cancer types most of the immune signatures analyzed were upregulated in the lower-TMB subtype, while in some other cancer types the immune signatures were prone to be upregulated in the higher-TMB subtype. However, the regulatory T cells, immune cell infiltrate, tumor-infiltrating lymphocytes, and cytokine signatures tended to be upregulated in the lower-TMB subtype, and the cancer-testis antigen (CTA) and pro-inflammatory signatures were inclined to be upregulated in the higher-TMB subtype. Importantly, high TMB was associated with elevated expression of PD-L1 in diverse prevailing cancers. Furthermore, we found that higher TMB was associated with better survival prognosis in numerous cancer types while was associated with worse prognosis in a few cancer types. High TMB may inhibit immune cell infiltrations while promote CTAs expression and inflammatory response in cancer. In many common cancer types, higher TMB may respond favorably to anti-PD-1/PD-L1 immunotherapy. Our data implicate that higher-TMB patients could gain a more favorable prognosis in diverse cancer types if treated with immunotherapy, otherwise would have a poorer prognosis compared to lower-TMB patients.

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将肿瘤突变负担与人类癌症的免疫特征相关联

肿瘤突变负荷（TMB）与癌症免疫治疗反应和癌症预后相关。尽管许多探索表明高TMB可能产生许多新抗原来激发抗肿瘤免疫反应，但缺乏对不同癌症类型中TMB与免疫特征之间相关性的系统探索。我们根据癌症基因组图谱 (TCGA) 的体细胞突变数据，将 32 种癌症类型分为低 TMB 亚型和高 TMB 亚型，并比较了免疫相关基因和基因集的表达水平每种癌症类型中两种癌症亚型之间的差异。在某些癌症类型中，大多数分析的免疫特征在较低 TMB 亚型中上调，而在其他一些癌症类型中，免疫特征在较高 TMB 亚型中易于上调。然而，调节性 T 细胞、免疫细胞浸润、肿瘤浸润淋巴细胞和细胞因子特征在较低 TMB 亚型中往往上调，而癌睾丸抗原 (CTA) 和促炎特征在低 TMB 亚型中往往上调。较高TMB 亚型。重要的是，高 TMB 与多种流行癌症中 PD-L1 表达升高相关。此外，我们发现较高的 TMB 与多种癌症类型的较好生存预后相关，而与少数癌症类型的较差预后相关。高 TMB 可能会抑制免疫细胞浸润，同时促进癌症中 CTA 的表达和炎症反应。在许多常见的癌症类型中，较高的 TMB 可能会对抗 PD-1/PD-L1 免疫疗法产生有利的反应。我们的数据表明，如果接受免疫疗法治疗，TMB 较高的患者可以在多种癌症类型中获得更有利的预后，否则与 TMB 较低的患者相比，预后会较差。