Sabine Tejpar教授专访
从CMS到IMF，肿瘤的诊断、预后预测将更为精准
第19届上海国际大肠癌高峰论坛于2023年6月17日在上海顺利召开。本次会议汇集了多位院士及海内外结直肠癌学术领军专家，围绕结直肠癌诊疗最新研究进展和方向展开学术汇报，可谓是精彩纷呈。【肿瘤资讯】小编亲临现场，特邀比利时鲁汶大学盖斯堡医院Dr. Sabine Tejpar接受专访，一同探讨共识分子亚型（CMS）及IMF分类在结直肠癌诊疗的进展与应用价值。
CMS的疗效预测作用、预后作用
Sabine Tejpar：至关重要的是，我们正尝试将预后作用与预测作用分开来看。正如你所提问的，共识分子亚型（CMS）对于化疗联合靶向治疗的预后作用已得以证实，但其疗效预测作用又会受到哪些因素的影响？
我认为有以下几个方面：首先，CMS的优点在于，它是一项全球性的结肠癌指标，基于批量转录组学，可重复性较强；但缺点是，它的通用性较强，未能精确到细胞类型。其次，CMS拥有全局性的分子标记物，这使得它在预后作用方面较为有力；然而，这样一种全局性标记物对于预测疗效的作用并不强。原因是，预测疗效的标志物需要极其精确，而非广泛。
那么，在疗效预测作用的精准标记物方面，我们该如何去做？第一，我们需要抛却旧的CMS，而使用内在的分子亚型，即判断上皮细胞的状态。从全局视角到精准地聚焦于上皮细胞，这对于疗效预测作用而言是一大进展。
目前，我们也正在进行免疫细胞的类似研究。因此，我们的视角并非像既往的CMS那样在所有的细胞，而是专注于某一类型的细胞，如上皮细胞、免疫细胞等。为达到上述目的，单细胞转录组学、空间转录组学、免疫组织化学等甚至更多的技术需要被掌握。
在过去，免疫细胞、上皮细胞等对于治疗的反应被隐藏在CMS广泛标记物中；但现在，由于分子生物学角度的精细化，这些免疫细胞、上皮细胞等的治疗反应将被观察到。既往，CMS得出的结论是，结肠癌有多种亚型；在今天，我们仍然秉持相同的结论，只是我们将使用显微镜对它们进行精确地观察。有了这一新层次的分型定义，疗效预测作用方面或将有所进展。
IMF分类的临床意义
Sabine Tejpar：在今天的演讲中，我已介绍过IMF的定义。我们正在进行的研究工作是更为详细的，这些还未发表。我们将上皮细胞及免疫细胞的细胞状态、细胞功能一一详尽阐述，我们还将细胞的状态及功能与药物反应联系起来。正如你所提问的，IMF相关研究的临床意义是什么？可以说，若医生开始思考这种更深层次的结肠癌分型，则说明他/她对于患者的肿瘤有了更精准的认识。
下一步，你将为你的患者提供一个良好的诊断：不仅是“结直肠癌”，而且是“某一个具体亚型的结直肠癌”。因此，IMF是第一步，为肿瘤的精准分层提供了工具。
第二步是，我们努力将IMF与药物治疗反应联系起来，从而有助于治疗决策的实行。目前IMF已经非常精确，为达到上述目的，我们似乎必须为每一种药物进行一次证实。
From CMS to IMF, Tumor Diagnosis and Prognosis Prediction Will Be More Accurate
The 19th Shanghai International Colorectal Cancer Forum was successfully held in Shanghai on June 17, 2023. The Forum brought together many academicians and leading experts in colorectal cancer at home and abroad to present the latest research progress and direction of colorectal cancer diagnosis and treatment, which can be described as wonderful. Dr. Sabine Tejpar from University Hospital Gasthuisberg, Leuven, Belgium was invited to be interviewed by the editor of Oncology News to discuss the progress and application value of CMS and IMF classification in colorectal cancer diagnosis and treatment.
Efficacy prediction, prognostic role of CMS
Sabine Tejpar：It is important that we are trying to separate the prognostic role from the predictive role. As you asked, the prognostic role of consensus molecular subtypes (CMS) for chemotherapy in combination with targeted therapy has been demonstrated, but what are the factors that influence its efficacy predictive role?
There are several parts: first, CMS has the advantage that it is a global colon cancer indicator, based on bulk transcriptomics, and is highly reproducible; however, the disadvantage is that it is more generalized and fails to be precise to cell type. Second, CMS has a global molecular marker, which makes it more powerful in terms of its prognostic role; however, such a global marker is not as useful for predicting efficacy. The reason for this is that markers for predicting efficacy need to be extremely precise, not broad.
So, where do we go from here in terms of precise markers for the predictive role of efficacy? First, we need to leave the old CMS behind and use the intrinsic molecular subtypes, i.e., determine the state of the epithelial cells. Moving from a global view to a precise focus on epithelial cells will be a major advance for efficacy prediction.
Currently, we are also conducting similar studies on immune cells. Therefore, our perspective is not in all cells as in the previous CMS, but we focus on a certain type of cells, such as epithelial cells, immune cells, etc. In order to achieve the above, single cell transcriptomics, spatial transcriptomics, immunohistochemistry and even more techniques need to be mastered.
In the past, the response of immune cells, epithelial cells, etc. to treatment was hidden in CMS extensive markers; but now, thanks to refinement from a molecular biology perspective, the response of these immune cells, epithelial cells, etc. to treatment will be observed. Previously, CMS concluded that there were multiple subtypes of colon cancer; today, we still hold the same conclusion, except that we will use microscopy to look at them precisely. With this new level of stratification definition, there may be progress in the predictive role of efficacy.
Clinical significance of IMF classification
Sabine Tejpar：In today's presentation, I have presented the IMF definition. Our ongoing research work is more detailed and these have not been published yet. We elaborate on the cellular state and cellular function of epithelial and immune cells, and we also relate the cellular state and function to drug response. As you asked, what are the clinical implications of IMF-related studies? It can be said that if a doctor starts to think about this deeper stratification of colon cancer, he/she has a more precise understanding of the patient's tumor.
The next step is to provide your patients with a good diagnosis: not only "colorectal cancer", but also "a specific subtype of colorectal cancer". Thus, IMF is the first step, providing a tool for precise tumor stratification.
The second step is our effort to correlate IMF with response to drug therapy, thereby making treatment decisions. The IMF is now so precise that, in order to achieve the above, it seems essential that we perform a confirmation for each drug.
排版编辑：肿瘤资讯-Lynn
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1. 1. Dienstmann, R., Vermeulen, L., Guinney, J. et al. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer 17, 79–92 (2017). https://doi.org/10.1038/nrc.2016.126
2. Lenz HJ, Ou FS, Venook AP,et al.Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2019 Aug 1;37(22):1876-1885. doi: 10.1200/JCO.18.02258.
3. Joanito I, Wirapati P, Zhao N,et al. Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer. Nat Genet. 2022 Jul;54(7):963-975. doi: 10.1038/s41588-022-01100-4.
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