Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
J Gastroenterol Hepatol. 2022 Mar;37(3):551-557. doi: 10.1111/jgh.15774. Epub 2022 Jan 25.
Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs.
Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups.
The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses.
The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.
肿瘤基质和肿瘤浸润淋巴细胞（TILs）是肿瘤微环境的主要组成部分，尽管它们对结直肠癌（CRC）患者的预后有不同的影响。肿瘤基质百分比（TSP）和 TILs 的联合状态有望提供更强大的预后信息，但从未在 CRC 中进行过研究。
使用计算机辅助方法评估 487 例接受辅助化疗的 III 期 CRC 患者的 TSP 和 CD3-TIL 或 CD8-TIL 密度。根据上皮内 TIL（iTIL）和基质 TIL（sTIL）密度的中位数设定截断值，将 CRC 分为低和高 iTIL 或 sTIL 组。根据 TSP 将 CRC 分为五个五分位数（Q1-Q5）组，并分为高 TSP（Q5）和低 TSP（Q1-4）组。
在多变量生存分析中，CD8 iTIL 密度和 TSP 的组合被发现是癌症特异性生存和无复发生存的独立预后参数。CD8 iTIL 密度低和 TSP 高的 CRC 患者的生存情况最差。联合状态比 CD8 iTIL 密度或 TSP 单独具有更高的预后能力。在 III 期 CRC 的独立队列中进行的多变量生存分析验证了联合状态的预后能力。
这些发现表明，联合状态可能是 III 期 CRC 的一个预后参数。需要在 III 期 CRC 的大样本患者队列中进一步研究，以验证联合状态的预后能力。
