Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer.
Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer.
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DOI：
10.1093/pnasnexus/pgad046
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Zanetti, Maurizio
中科院分区：
文献类型：
--
作者：
Xian, Su;Dosset, Magalie;Castro, Andrea;Carter, Hannah;Zanetti, Maurizio
端粒酶逆转录酶（TERT）是一种保守的自体肿瘤抗原，在约85%的肿瘤细胞中过表达，在癌症患者中具有免疫原性。TERT表达在调节肿瘤内适应性免疫中的作用尚未被研究。我们使用来自11种实体肿瘤类型的癌症基因组图谱（TCGA）的RNA测序数据来研究肿瘤微环境中TERT表达与B细胞和T细胞浸润之间的潜在相互作用。我们发现TERT表达与B和T细胞在四种癌症类型中呈正相关，其中在头颈部鳞状细胞癌（HSNCC）中相关性最强。在HNSCC中，Bhigh/TERThigh特征与改善的无进展生存期（PFS）相关（P = 0.0048）。这种效应与HPV状态无关，并且在其他保守的肿瘤抗原（NYESO1、MUC1、MAGE和CEA）的比较分析中没有共享。Bhigh/TERThigh HNSCC肿瘤也有三级淋巴结构（TLS）的证据，如生发中心（GC）和开关记忆B细胞、中枢记忆CD4和效应记忆CD8 T细胞的特征。Bhigh/TERThigh HNSCC肿瘤还表现出与B和T细胞活化、增殖、迁移和细胞毒性相关的基因和通路的上调，而与免疫抑制和癌细胞侵袭性相关的因子则下调。总之，我们的研究揭示了HNSCC中高TERT表达与高B细胞浸润之间的新关联，表明激活TERT介导的肿瘤内T-B合作的治疗策略可能会带来潜在的益处。
Telomerase reverse transcriptase (TERT) is a conserved self-tumor antigen overexpressed in ∼85% of tumor cells and is immunogenic in cancer patients. The effect of TERT expression on the regulation of intratumor adaptive immunity has not yet been investigated. We used RNA sequencing data from The Cancer Genome Atlas (TCGA) in 11 solid tumor types to investigate potential interactions between TERT expression, and B and T cell infiltrate in the tumor microenvironment. We found a positive correlation between TERT expression, B and T cells in four cancer types with the strongest association in head and neck squamous cell carcinoma (HSNCC). In HNSCC a Bhigh/TERThigh signature was associated with improved progression-free survival (PFS) (P = 0.0048). This effect was independent of HPV status and not shared in comparable analysis by other conserved tumor antigens (NYESO1, MUC1, MAGE, and CEA). Bhigh/TERThigh HNSCC tumors also harbored evidence of tertiary lymphoid structure (TLS) such as signatures for germinal center (GC) and switched memory B cells, central memory CD4 and effector memory CD8 T cells. Bhigh/TERThigh HNSCC tumors also showed an up-regulation of genes and pathways related to B and T cell activation, proliferation, migration, and cytotoxicity, while factors associated with immunosuppression and cancer cell invasiveness were down-regulated. In summary, our study uncovers a new association between high TERT expression and high B cell infiltrate in HNSCC, suggesting a potential benefit from therapeutic strategies that invigorate intratumor TERT-mediated T-B cooperation.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
DOI：
10.1084/jem.20091472
发表时间：
2009-11-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Halle S;Dujardin HC;Bakocevic N;Fleige H;Danzer H;Willenzon S;Suezer Y;Hämmerling G;Garbi N;Sutter G;Worbs T;Förster R
通讯作者：
Förster R
影响因子：
3.5
作者：
Daniel M;Peek GW;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
10.3
作者：
Fakhry, Carole;Westra, William H.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.