文章來源：醫脈通
2015年ASCO年會于5月29日—6月2日在美國芝加哥召開。5月30日下午消化系統（結直腸）腫瘤口頭報告專場上，摘要號為3506的一項研究利用結直腸癌綜合分子特征揭露了免疫細胞浸潤的基因組預測。醫脈通整理如下：
結直腸癌（CRC）是一種在復雜的微環境中起病與進展的分子異質性疾病。腫瘤免疫細胞的浸潤已被證實與CRC特異性和總生存率的提高相關。然而，CRC決定免疫浸潤數量與類型的基因組特征在很大程度上尚未明確。
研究方法：
研究人員從兩組大型前瞻性隊列研究（護士健康研究和醫務人員追蹤研究）中選取了689例原發結直腸癌患者（pts）進行了全基因組測序和微衛星不穩定性（MSI）分析。用免疫組織化的方法標記了免疫浸潤的特征（瘤周，瘤內腺體周圍，Crohn''s狀，腫瘤浸潤，和總淋巴細胞評分），同時對T細胞亞群（CD3+，CD8+，CD45RO+，FoxP3+）進行了組織微陣列成像分析。他們利用一種新的計算途徑來計算腫瘤新抗原負荷（由體細胞突變產生的多肽，被免疫系統識別為異物），隨后將腫瘤新抗原負荷與上述免疫變量和患者生存相關聯。
研究結果：
相較于微衛星穩定腫瘤，微衛星高度不穩定的腫瘤明顯會表達更多的新抗原（P＜2e-16）。在原發結直腸癌患者中，腫瘤新抗原負荷與總淋巴細胞評分（P=4.9e-9）和腫瘤浸潤淋巴細胞（P=1.6e-15）顯著相關。在T細胞亞群的分析中，腫瘤新抗原負荷僅與CD45RO+ T細胞亞群（P=0.0003）顯著相關。腫瘤新抗原負荷越高預示著CRC特異性和總生存率更高（分別為P=0.014，P=0.048）。
結論：
本項大型前瞻性CRC分子特征的研究顯示，腫瘤新抗原負荷預示著更多的腫瘤浸潤淋巴細胞和記憶性T細胞浸潤，可作為CRC患者生存的新型基因組預測指標。本研究將腫瘤基因組學與特定免疫反應元素相關聯，對以后CRC的治療決策有一定的影響。
會議專題》》》2015年ASCO年會專題報道
閱讀摘要原文：
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.