中国对三阴性乳腺癌免疫分型施策
既往研究已经证实，肿瘤免疫微环境对于患者预后和免疫治疗具有显著影响。不过，三阴性乳腺癌的免疫微环境特征尚不明确。
2019年3月5日，美国癌症研究协会《临床癌症研究》在线发表复旦大学附属肿瘤医院、复旦大学公共卫生学院、国家人类基因组南方研究中心、上海产业技术研究院、中国科学院上海高等研究院干细胞与纳米医学研究中心、中国科学院上海生命科学研究院、上海科学院、法国马赛癌症研究所的研究报告，通过大样本多组学分析揭示了三阴性乳腺癌独有的微环境特征，并且发现了三阴性乳腺癌的免疫逃逸机制。
该单中心研究对2007年1月1日～2017年12月31日复旦大学附属肿瘤医院乳腺外科连续386例三阴性乳腺癌女性患者的原始多组学数据集进行了免疫原性广泛分析，以探讨三阴性乳腺癌微环境的不同特征和预后意义，并且进一步分析了三阴性乳腺癌的潜在免疫逃逸机制。
结果，该研究发现三阴性乳腺癌微环境表现特征可以分为三个不同类型：
免疫沙漠型：微环境细胞浸润率较低。
免疫失活型：先天免疫细胞静息、无免疫基质细胞浸润。
免疫炎症型：后天和先天免疫细胞浸润丰富
对于上述结果，该研究通过病理切片进行了内部验证、通过美国癌症基因组图谱（TCGA）和国际乳腺癌分子分类联盟（METABRIC）患者队列进行了外部验证，证实微环境分型的预后效果显著。潜在免疫逃逸机制分析结果表明：
免疫沙漠型：无法吸引免疫细胞，而且与MYC基因扩增相关。
免疫失活型：存在趋化作用，但是先天免疫失活和肿瘤抗原量较少可能有助于免疫逃逸，并且可能与PI3K→AKT通路基因突变相关。
免疫炎症型：免疫检查点分子高表达。
因此，该研究结果有助于三阴性乳腺癌患者的个体化免疫治疗。对于免疫炎症型三阴性乳腺癌，免疫检查点抑制剂可能有效；对于免疫沙漠型和免疫失活型三阴性乳腺癌，应该考虑将“免疫冷淡型肿瘤”转变为“免疫热情型肿瘤”。
相关阅读
Clin Cancer Res. 2019 Mar 5. [Epub ahead of print]
Multi-omics profiling reveals distinct microenvironment characterization and suggests immune escape mechanisms of triple-negative breast cancer.
Xiao Y, Ma D, Zhao S, Suo C, Shi J, Xue MZ, Ruan M, Wang H, Zhao J, Li Q, Wang P, Shi L, Yang WT, Huang W, Hu X, Yu K, Huang S, Bertucci F, Jiang YZ, Shao ZM.
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences; School of Public Health, Fudan University; Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI); SARI Center for Stem Cell and Nanomedicine, Chinese Academy of Sciences; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Chinese National Human Genome Center and Shanghai Academy of Science and Technology; Institute Paoli-Calmettes.
PURPOSE: The tumor microenvironment has a profound impact on prognosis and immunotherapy. However, the landscape of the triple-negative breast cancer (TNBC) microenvironment has not been fully understood.
EXPERIMENTAL DESIGN: Using the largest original multi-omics dataset of TNBC (n = 386), we conducted an extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TNBC microenvironment. We further analyzed the potential immune escape mechanisms of TNBC.
RESULTS: The TNBC microenvironment phenotypes were classified into three heterogeneous clusters: cluster 1, the "immune-desert" cluster, with low microenvironment cell infiltration; cluster 2, the "innate immune-inactivated" cluster, with resting innate immune cells and nonimmune stromal cells infiltration; and cluster 3, the "immune-inflamed" cluster, with abundant adaptive and innate immune cells infiltration. The clustering result was validated internally with pathological sections and externally with TCGA and METABRIC cohorts. The microenvironment clusters had significant prognostic efficacy. In terms of potential immune escape mechanisms, cluster 1 was characterized by an incapability to attract immune cells, and MYC amplification was correlated with low immune infiltration. In cluster 2, chemotaxis but inactivation of innate immunity and low tumor antigen burden might contribute to immune escape, and mutations in the PI3K-AKT pathway might be correlated with this effect. Cluster 3 featured high expression of immune checkpoint molecules.
CONCLUSIONS: Our study represents a step towards personalized immunotherapy for TNBC patients. Immune checkpoint inhibitors might be effective for "immune-inflamed" cluster, and the transformation of "cold tumors" into "hot tumors" should be considered for "immune-desert" and "innate immune-inactivated" clusters.
PMID: 30837276
PII: clincanres.3524.2018
DOI: 10.1158/1078-0432.CCR-18-3524
以下广告内容与本微信公众号无关