文章来源：医脉通
2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月30日下午消化系统（结直肠）肿瘤口头报告专场上，摘要号为3506的一项研究利用结直肠癌综合分子特征揭露了免疫细胞浸润的基因组预测。医脉通整理如下：
结直肠癌（CRC）是一种在复杂的微环境中起病与进展的分子异质性疾病。肿瘤免疫细胞的浸润已被证实与CRC特异性和总生存率的提高相关。然而，CRC决定免疫浸润数量与类型的基因组特征在很大程度上尚未明确。
研究方法：
研究人员从两组大型前瞻性队列研究（护士健康研究和医务人员追踪研究）中选取了689例原发结直肠癌患者（pts）进行了全基因组测序和微卫星不稳定性（MSI）分析。用免疫组织化的方法标记了免疫浸润的特征（瘤周，瘤内腺体周围，Crohn''s状，肿瘤浸润，和总淋巴细胞评分），同时对T细胞亚群（CD3+，CD8+，CD45RO+，FoxP3+）进行了组织微阵列成像分析。他们利用一种新的计算途径来计算肿瘤新抗原负荷（由体细胞突变产生的多肽，被免疫系统识别为异物），随后将肿瘤新抗原负荷与上述免疫变量和患者生存相关联。
研究结果：
相较于微卫星稳定肿瘤，微卫星高度不稳定的肿瘤明显会表达更多的新抗原（P＜2e-16）。在原发结直肠癌患者中，肿瘤新抗原负荷与总淋巴细胞评分（P=4.9e-9）和肿瘤浸润淋巴细胞（P=1.6e-15）显著相关。在T细胞亚群的分析中，肿瘤新抗原负荷仅与CD45RO+ T细胞亚群（P=0.0003）显著相关。肿瘤新抗原负荷越高预示着CRC特异性和总生存率更高（分别为P=0.014，P=0.048）。
结论：
本项大型前瞻性CRC分子特征的研究显示，肿瘤新抗原负荷预示着更多的肿瘤浸润淋巴细胞和记忆性T细胞浸润，可作为CRC患者生存的新型基因组预测指标。本研究将肿瘤基因组学与特定免疫反应元素相关联，对以后CRC的治疗决策有一定的影响。
会议专题》》》2015年ASCO年会专题报道
阅读摘要原文：
Comprehensive molecular characterization of colorectal cancer reveals genomic predictors of immune cell infiltrates.（Abstract 3505）
Authors：Marios Giannakis, Sachet Shukla，et al.
Session Type：Oral Abstract Session
Background：Colorectal cancer (CRC) is a molecularly heterogeneous disease that arises and progresses in the context of a complex microenvironment. Tumor immune cell infiltrates have been shown to be associated with an improved CRC-specific and overall survival. However, the genomic features of CRC that determine the number and types of immune infiltrates remain largely uncharacterized.
Methods：We performed Whole Exome Sequencing and microsatellite instability (MSI) analysis on primary CRCs from 689 patients (pts) identified from two large prospective cohorts, the Nurses’ Health Study and the Health Professionals Follow-Up Study. We also immunohistochemically characterized the immune infiltrate (peritumoral, intratumoral periglandular, Crohn’s-like, tumor-infiltrating, and total lymphocyte score) and conducted tissue microarray imaging analysis for T-cell subsets (CD3+, CD8+, CD45RO+, FoxP3+). We utilized a novel computational pipeline to calculate tumor neoantigen load (peptides resulting from somatic mutations and recognized by the immune system as foreign) and subsequently correlated the tumor neoantigen load with the aforementioned immune variables and with pt survival.
Results：When compared to microsatellite-stable cancers, MSI-high tumors expressed significantly more neoantigens (P < 2e-16). Tumor neoantigen load significantly correlated with total lymphocytic score in the primary CRCs (P = 4.9e-9) and was most significantly associated with tumor infiltrating lymphocytes (P = 1.6e-15). Among T-cell subsets, tumor neoantigen load was only significantly associated with the CD45RO+ T-cell subset (P = 0.0003). Higher tumor neoantigen load predicted significantly improved CRC-specific and overall survival (P = 0.014 and P = 0.048, respectively).
Conclusions：In the large prospective study of molecularly characterized CRCs, tumor neoantigen load predicts greater tumor-infiltrating lymphocytes and memory T-cell infiltration and represents a novel genomic predictor of CRC survival. Our findings link tumor genomics to specific immune response elements and have implications for the therapeutic manipulation of the latter in CRC.