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Human Leukocyte Antigen (HLA) expression contributes to the activation of anti-tumor immunity through interactions with T cell receptors. Pan-cancer HLA-mediated immunogenicity and immunoediting mechanisms have not been systematically studied previously. In a retrospective analysis of 33 tumor types from the Cancer Genome Atlas (TCGA), we characterized the differential expression of HLA class I and class II genes across various oncogenic pathways and immune subtypes. While HLA I genes were upregulated in all immunogenically hot tumors, HLA II genes were upregulated in an inflammatory immune subtype associated with best prognosis and were systematically downregulated in specific oncogenic pathways. A subset of immunogenically hot tumors which upregulated HLA class I but not class II genes exploited HLA-mediated escape strategies. Furthermore, with a machine learning model, we demonstrated that HLA gene expression data can be used to predict the immune subtypes of patients receiving immune checkpoint blockade and stratify patient survival. Interestingly, tumors with the highest immune infiltration did not have the best prognosis but showed significantly higher immune exhaustion. Implications: Taken together, we highlight the prognostic potential of HLA genes in immunotherapies and suggest that higher tumor immunogenicity mediated by HLA expression may sometimes lead to tumor escape under strong selective pressure.

A qualitative and quantitative analysis of metabolites was performed by metabolomics comparation on the pericarps of four varieties of Zanthoxylum bungeanum Maxim. The Zanthoxylum bunganum as scion combined with three rootstock varieties of Zanthoxylum piasezkii Maxim (YJ), July Zanthoxylum bunganum Maxim (QJ), and August Zanthoxylum bunganum Maxim (BJ), at the same time Zanthoxylum bungeanum seedlings breeding were compared as control (MJ). A total of 1429 metabolites were identified in Zanthoxylum bungeanum Maxim pericarps based on chromatography and mass spectrometry dual detection platform. While the metabolites between four varieties of Z. bungeanum varied, there was identified 31, 15, 7, 79, 42, 19 down-regulated and 55, 50, 13, 75, 43, 27 up-regulated differential metabolites between MJ and BJ, MJ and QJ, MJ and YJ, QJ and BJ, YJ and BJ, YJ and QJ. Meanwhile, the differential metabolites composition was distinct among various varieties of Z. bungeanum and dominant by phenolic compounds flavonoid and phenolic acids, especially highest in varieties July Zanthoxylum bunganum Maxim. Highlight A comparative metabolomics analyzed in four varieties of Zanthoxylum bungeanum pericarp.Total 1429 metabolites were identified and mainly in flavonoid and phenolic acid.July and August Zanthoxylum bunganum Maxim has highest antioxidant capacity.The rootstock July Zanthoxylum bunganum Maxim was recommended in Loess Plateau.

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