Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC
BackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004345/full |
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| author | Ting Deng Huiya Wang Changliang Yang Mengsi Zuo Zhi Ji Ming Bai Tao Ning Rui Liu Junyi Wang Shaohua Ge Le Zhang Yi Ba Haiyang Zhang |
| author_facet | Ting Deng Huiya Wang Changliang Yang Mengsi Zuo Zhi Ji Ming Bai Tao Ning Rui Liu Junyi Wang Shaohua Ge Le Zhang Yi Ba Haiyang Zhang |
| author_sort | Ting Deng |
| collection | DOAJ |
| description | BackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer.ResultsThe transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB.ConclusionsThis study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer. |
| first_indexed | 2024-04-12T08:52:53Z |
| format | Article |
| id | doaj.art-79dc246d7c22424cae5c1e9ca3400c9e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T08:52:53Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-79dc246d7c22424cae5c1e9ca3400c9e2022-12-22T03:39:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10043451004345Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCCTing DengHuiya WangChangliang YangMengsi ZuoZhi JiMing BaiTao NingRui LiuJunyi WangShaohua GeLe ZhangYi BaHaiyang ZhangBackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer.ResultsThe transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB.ConclusionsThis study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004345/fullsingle cell sequencingPD-1 mMABperipheral bloodimmune cellsESCC |
| spellingShingle | Ting Deng Huiya Wang Changliang Yang Mengsi Zuo Zhi Ji Ming Bai Tao Ning Rui Liu Junyi Wang Shaohua Ge Le Zhang Yi Ba Haiyang Zhang Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC Frontiers in Immunology single cell sequencing PD-1 mMAB peripheral blood immune cells ESCC |
| title | Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC |
| title_full | Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC |
| title_fullStr | Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC |
| title_full_unstemmed | Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC |
| title_short | Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC |
| title_sort | single cell sequencing revealed the mechanism of pd 1 resistance affected by the expression profile of peripheral blood immune cells in escc |
| topic | single cell sequencing PD-1 mMAB peripheral blood immune cells ESCC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1004345/full |
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