DataSheet_1_Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy.docx

Accurate immune molecular typing is pivotal for screening out patients with colon adenocarcinoma (COAD) who may benefit from immunotherapy and whose tumor microenvironment (TME) was needed for reprogramming to beneficial immune-mediated responses. However, little is known about the immune characteristic of COAD. Here, by calculating the enrichment score of immune characteristics in three online COAD datasets (TCGA-COAD, GSE39582, and GSE17538), we identified 17 prognostic-related immune characteristics that overlapped in at least two datasets. We determined that COADs could be stratified into three immune subtypes (IS1–IS3), based on consensus clustering of these 17 immune characteristics. Each of the three ISs was associated with distinct clinicopathological characteristics, genetic aberrations, tumor-infiltrating immune cell composition, immunophenotyping (immune “hot” and immune “cold”), and cytokine profiles, as well as different clinical outcomes and immunotherapy/therapeutic response. Patients with the IS1 tumor had high immune infiltration but immunosuppressive phenotype, IS3 tumor is an immune “hot” phenotype, whereas those with the IS2 tumor had an immune “cold” phenotype. We further verified the distinct immune phenotype of IS1 and IS3 by an in-house COAD cohort. We propose that the immune subtyping can be utilized to identify COAD patients who will be affected by the tumor immune microenvironment. Furthermore, the ISs may provide a guide for personalized cancer immunotherapy and for tumor prognosis.

精准的免疫分子分型对于筛选出可从免疫治疗中获益的结肠腺癌（colon adenocarcinoma, COAD）患者至关重要，且其肿瘤微环境（tumor microenvironment, TME）需被重编程以诱导有益的免疫介导应答，这亦是该分型的核心前提。然而，目前针对COAD的免疫特征仍知之甚少。本研究通过计算3个公开COAD数据集（TCGA-COAD、GSE39582及GSE17538）中免疫特征的富集得分，筛选出了至少在2个数据集中重复出现的17种预后相关免疫特征。基于这17种免疫特征的一致性聚类分析，我们将COAD划分为3种免疫亚型（immune subtypes, IS1–IS3）。这3种免疫亚型各自对应独特的临床病理特征、遗传畸变、肿瘤浸润免疫细胞组成、免疫表型（免疫"热型"与免疫"冷型"）及细胞因子谱，同时也关联着不同的临床结局与免疫治疗响应情况。其中，IS1型肿瘤呈现高免疫浸润但伴随免疫抑制表型，IS3型肿瘤属于免疫"热型"表型，而IS2型肿瘤则为免疫"冷型"表型。我们进一步通过自建COAD队列验证了IS1与IS3亚型的独特免疫表型。本研究提出，免疫分型可用于识别受肿瘤免疫微环境影响的COAD患者。此外，上述免疫亚型可为癌症个性化免疫治疗及肿瘤预后评估提供参考依据。