文章來(lái)源：醫(yī)脈通
2015年ASCO年會(huì)于5月29日—6月2日在美國(guó)芝加哥召開(kāi)。5月30日下午消化系統(tǒng)（結(jié)直腸）腫瘤口頭報(bào)告專(zhuān)場(chǎng)上，摘要號(hào)為3506的一項(xiàng)研究利用結(jié)直腸癌綜合分子特征揭露了免疫細(xì)胞浸潤(rùn)的基因組預(yù)測(cè)。醫(yī)脈通整理如下：
結(jié)直腸癌（CRC）是一種在復(fù)雜的微環(huán)境中起病與進(jìn)展的分子異質(zhì)性疾病。腫瘤免疫細(xì)胞的浸潤(rùn)已被證實(shí)與CRC特異性和總生存率的提高相關(guān)。然而，CRC決定免疫浸潤(rùn)數(shù)量與類(lèi)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(duì)列研究（護(hù)士健康研究和醫(yī)務(wù)人員追蹤研究）中選取了689例原發(fā)結(jié)直腸癌患者（pts）進(jìn)行了全基因組測(cè)序和微衛(wèi)星不穩(wěn)定性（MSI）分析。用免疫組織化的方法標(biāo)記了免疫浸潤(rùn)的特征（瘤周，瘤內(nèi)腺體周?chē)?，Crohn''s狀，腫瘤浸潤(rùn)，和總淋巴細(xì)胞評(píng)分），同時(shí)對(duì)T細(xì)胞亞群（CD3+，CD8+，CD45RO+，F(xiàn)oxP3+）進(jìn)行了組織微陣列成像分析。他們利用一種新的計(jì)算途徑來(lái)計(jì)算腫瘤新抗原負(fù)荷（由體細(xì)胞突變產(chǎn)生的多肽，被免疫系統(tǒng)識(shí)別為異物），隨后將腫瘤新抗原負(fù)荷與上述免疫變量和患者生存相關(guān)聯(lián)。
研究結(jié)果：
相較于微衛(wèi)星穩(wěn)定腫瘤，微衛(wèi)星高度不穩(wěn)定的腫瘤明顯會(huì)表達(dá)更多的新抗原（P＜2e-16）。在原發(fā)結(jié)直腸癌患者中，腫瘤新抗原負(fù)荷與總淋巴細(xì)胞評(píng)分（P=4.9e-9）和腫瘤浸潤(rùn)淋巴細(xì)胞（P=1.6e-15）顯著相關(guān)。在T細(xì)胞亞群的分析中，腫瘤新抗原負(fù)荷僅與CD45RO+ T細(xì)胞亞群（P=0.0003）顯著相關(guān)。腫瘤新抗原負(fù)荷越高預(yù)示著CRC特異性和總生存率更高（分別為P=0.014，P=0.048）。
結(jié)論：
本項(xiàng)大型前瞻性CRC分子特征的研究顯示，腫瘤新抗原負(fù)荷預(yù)示著更多的腫瘤浸潤(rùn)淋巴細(xì)胞和記憶性T細(xì)胞浸潤(rùn)，可作為CRC患者生存的新型基因組預(yù)測(cè)指標(biāo)。本研究將腫瘤基因組學(xué)與特定免疫反應(yīng)元素相關(guān)聯(lián)，對(duì)以后CRC的治療決策有一定的影響。
會(huì)議專(zhuān)題》》》2015年ASCO年會(huì)專(zhuān)題報(bào)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.