Characterization of the Intra-tumoral B Cell Immunoglobulin Repertoire Is of Prognostic Value for Esophageal Squamous Cell Carcinoma.
Characterization of the Intra-tumoral B Cell Immunoglobulin Repertoire Is of Prognostic Value for Esophageal Squamous Cell Carcinoma.
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肿瘤内B细胞免疫球蛋白库的表征对食管鳞状细胞癌具有预后价值。
DOI：
10.3389/fimmu.2022.896627
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
食道鳞状细胞癌(ESCC)是一种高度异质性的恶性肿瘤，是全球癌症相关死亡的主要原因之一。B细胞在免疫防御系统和肿瘤的进展和消退中发挥着关键作用，但肿瘤浸润性B细胞(TIB)及其与临床预后的关系在ESCC中仍未被探索。在这里，我们收集了119个ESCC肿瘤的大量RNA-seq测序数据，并与邻近的正常样本进行匹配，以描绘B细胞谱系。我们发现，与激活的T细胞相比，ESCC更多地被B细胞和浆细胞侵袭。免疫球蛋白重链可变区(IGHV)基因在食管鳞癌中的表达明显偏低，IGHV3-74在食管鳞癌中表达不足。TIB表现出更多的寡克隆性，伴随着广泛的克隆性扩张和Ig G亚类转换事件(CSR)。生存分析揭示了肿瘤浸润性B细胞与预后之间的几个意想不到的关联。较高水平的免疫球蛋白表达(IgH)、CD138表达、IgH/MS4A1比率、CSR事件和克隆多样性都与较好的生存相关。值得注意的是，我们发现CD20阴性的产生免疫球蛋白G2的浆细胞的丰度对总体生存有很强的积极影响，风险比(HR)为0.4(对数等级p：0.002)。结合分子亚型，产生免疫球蛋白G2的浆细胞可以更准确地对高危患者进行分层，HR为0.253(对数等级p：0.0006)。保护性B细胞群与ESCC预后之间的直接联系为高危患者的选择提供了生物标志物，并为发展针对ESCC患者B细胞的免疫治疗策略提供了巨大的希望。
Esophageal Squamous Cell carcinomas (ESCC) is a highly heterogeneous malignancy that is among the leading cause of cancer-related death worldwide. B cells play pivotal roles in the immune defense system and cancer progression and regression, yet the repertoire of tumor infiltrating B cells (TIBs) and its association with clinical outcome remains unexplored in ESCC. Here we collected bulk RNA-seq sequencing data from 119 ESCC tumors and matched adjacent normal samples to delineate the B cell repertoire. We found that ESCC is more heavily infiltrated by B cells and plasma cells compared to activated T cells. The immunoglobulin heavy chain variable region (IGHV) gene usage was remarkably biased and IGHV3-74 was under-represented in ESCC tumors. The TIBs showed a more oligoclonal profile along with widespread clonal expansion and IgG subclass switch events (CSRs). Survival analysis revealed several unexpected associations between tumor infiltrating B cells and prognosis. Higher levels of immunoglobulin expression (IGH), CD138 expression, IGH to MS4A1 ratio, CSR events and clone diversity are all associated with better survival. Notably, we found that the abundance of CD20-negative IgG2-producing plasma cells has a strong positive effect on overall survival with a hazard ratio (HR) of 0.40 (log-rank p: 0.002). Combing molecular subtyping, the IgG2-producing plasma cells could stratify high-risk patients more accurately with a HR of 0.253 (log-rank p: 0.0006). The direct link between protective B cell populations and ESCC prognosis provides biomarkers for high-risk patient selection and holds great promise for developing strategies for immunotherapy targeting B cells in ESCC patients.
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影响因子：
46.9
作者：
Bolotin DA;Poslavsky S;Davydov AN;Frenkel FE;Fanchi L;Zolotareva OI;Hemmers S;Putintseva EV;Obraztsova AS;Shugay M;Ataullakhanov RI;Rudensky AY;Schumacher TN;Chudakov DM
通讯作者：
Chudakov DM
DOI：
10.1093/biostatistics/kxr054
发表时间：
2012-04
期刊：
Biostatistics (Oxford, England)
影响因子：
--
作者：
Hansen KD;Irizarry RA;Wu Z
通讯作者：
Wu Z
影响因子：
7.7
作者：
Horns, Felix;Vollmers, Christopher;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
12.8
作者：
Garcia-Alvarez, Maria;Alonso-Alvarez, Sara;Alcoceba, Miguel
通讯作者：
Alcoceba, Miguel
影响因子：
8.8
作者：
Ellebrecht CT;Mukherjee EM;Zheng Q;Choi EJ;Reddy SG;Mao X;Payne AS
通讯作者：
Payne AS