Stoll Gautier, Pol Jonathan, Soumelis Vassili, Zitvogel Laurence, Kroemer Guido
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
Oncoimmunology. 2018 Aug 6;7(10):e1484980. doi: 10.1080/2162402X.2018.1484980. eCollection 2018.
Multiple soluble factors including proteins (in particular chemokines), non-proteinaceous factors released by dead cells, as well as receptors for such factors (in particular chemokine receptors, formyl peptide receptors and purinergic receptors), influence the recruitment of distinct cell subsets into the tumor microenvironment. We performed an extensive bioinformatic analysis on tumor specimens from 5953 cancer patients to correlate the mRNA expression levels of chemotactic factors/receptors with the density of immune cell types infiltrating the malignant lesions. This meta-analysis, which included specimens from breast, colorectal, lung, ovary and head and neck carcinomas as well as melanomas, revealed that a subset of chemotactic factors/receptors exhibited a positive and reproducible correlation with several infiltrating cell types across various solid cancers, revealing a universal pattern of association. Hence, this meta-analysis distinguishes between homogeneous associations that occur across different cancer types and heterogeneous correlations, that are specific of one organ. Importantly, in four out of five breast cancer cohorts for which clinical data were available, the levels of expression of chemotactic factors/receptors that exhibited universal (rather than organ-specific) positive correlations with the immune infiltrate had a positive impact on the response to neoadjuvant chemotherapy. These results support the notion that general (rather than organ-specific) rules governing the recruitment of immune cells into the tumor bed are particularly important in determining local immunosurveillance and response to therapy.
多种可溶性因子，包括蛋白质（特别是趋化因子）、死亡细胞释放的非蛋白质因子以及这些因子的受体（特别是趋化因子受体、甲酰肽受体和嘌呤能受体），影响不同细胞亚群向肿瘤微环境的募集。我们对来自5953名癌症患者的肿瘤标本进行了广泛的生物信息学分析，以将趋化因子/受体的mRNA表达水平与浸润恶性病变的免疫细胞类型密度相关联。这项荟萃分析包括来自乳腺癌、结直肠癌、肺癌、卵巢癌和头颈癌以及黑色素瘤的标本，结果显示，趋化因子/受体的一个子集与各种实体癌中的几种浸润细胞类型呈现出正相关且可重复的关联，揭示了一种普遍的关联模式。因此，这项荟萃分析区分了不同癌症类型中出现的同质关联和特定于一个器官的异质关联。重要的是，在有临床数据的五分之四的乳腺癌队列中，与免疫浸润呈现普遍（而非器官特异性）正相关的趋化因子/受体的表达水平对新辅助化疗的反应有积极影响。这些结果支持这样一种观点，即在确定局部免疫监视和对治疗的反应方面，控制免疫细胞募集到肿瘤床的一般（而非器官特异性）规则尤为重要。
