The head and neck cancer immune landscape and its immunotherapeutic implications
The head and neck cancer immune landscape and its immunotherapeutic implications
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DOI：
10.1172/jci.insight.89829
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发表时间：
2016-10-20
期刊：
影响因子：
8
通讯作者：
Morris, Luc G. T.
中科院分区：
文献类型：
--
作者：
Mandal, Rajarsi;Senbabaoglu, Yasin;Morris, Luc G. T.
最近的临床试验表明，接受免疫检查点阻断治疗的晚期头颈部鳞状细胞癌(HNSCC)患者具有明显的生存优势。这些新出现的结果表明，HNSCC是免疫治疗研究中最有前途的前沿之一。然而，头颈部免疫肿瘤学的进一步发展需要对这些肿瘤中发现的免疫浸润性情况有详细的了解。我们利用癌症基因组图谱(TCGA)描述的280个肿瘤的转录组数据来全面描述HNSCC的免疫状况，以便为HNSCC的免疫治疗策略制定理论基础并指导临床研究。我们发现，HPV+和HPV-HNSCC肿瘤都是免疫力最强的浸润性癌症类型。值得注意的是，在我们对免疫浸润率最高的肿瘤的泛癌分析中，HNSCC的Treg/CD8(+)T细胞中值比率和CD56(Dim)NK细胞的浸润率都是最高的。CD8(+)T细胞浸润和CD56(Dim)NK细胞浸润均与HNSCC的生存有关。携带基因吸烟特征的肿瘤免疫渗透较低，与较差的存活率相关，这表明这些患者可能从免疫激动剂治疗中受益。这些发现阐明了HPV+和HPV-HNSCC的免疫格局。此外，这一前景为研究针对Tregs(例如CTLA-4、GITR、ICOS、IDO和VEGFA)和NK细胞(例如KIR、TIGIT和4-1BB)的调节剂作为抗PD-1的辅助治疗晚期HNSCC提供了潜在的新的理论基础。
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation. We find that both HPV+ and HPV- HNSCC tumors are among the most highly immune-infiltrated cancer types. Strikingly, HNSCC had the highest median Treg/CD8(+) T cell ratio and the highest levels of CD56(dim) NK cell infiltration, in our pan-cancer analysis of the most immune-infiltrated tumors. CD8(+) T cell infiltration and CD56(dim) NK cell infiltration each correlated with superior survival in HNSCC. Tumors harboring genetic smoking signatures had lower immune infiltration and were associated with poorer survival, suggesting these patients may benefit from immune agonist therapy. These findings illuminate the immune landscape of HPV+ and HPV- HNSCC. Additionally, this landscape provides a potentially novel rationale for investigation of agents targeting modulators of Tregs (e.g., CTLA-4, GITR, ICOS, IDO, and VEGFA) and NK cells (e g., KIR, TIGIT, and 4-1BB) as adjuncts to anti-PD-1 in the treatment of advanced HNSCC.