Flaherty Devin C, Lavotshkin Simon, Jalas John R, Torisu-Itakura Hitoe, Kirchoff Daniel D, Sim Myung S, Lee Delphine J, Bilchik Anton J
Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Department of Pathology, Providence Saint John's Health Center, Santa Monica, CA.
J Am Coll Surg. 2016 Jul;223(1):134-40. doi: 10.1016/j.jamcollsurg.2016.03.003. Epub 2016 Mar 18.
Retrospective data indicate that immunoprofiling of T cell markers can be prognostic in colon cancer. Prospective T cell immunoprofiling of colon cancer has not been well defined for patients whose lymph nodes are ultrastaged.
A prospective cohort was selected from patients enrolled in an ongoing phase II multicenter trial of nodal ultrastaging for colon cancer. Primary tumor specimens from 89 patients were analyzed by immunohistochemistry for the T cells CD3(+), CD4(+), CD8(+), and FOXP3(+). Lymphocyte populations were quantified with digital image analysis. Results were examined for their association with 5-year disease-free survival along with TNM stage and clinicopathologic variables.
Longer disease-free survival was associated with higher CD3(+) counts at the invasive margin (IM) (p = 0.005), higher CD8(+) counts at the tumor center (TC) and IM (p = 0.002), a lower CD4(+)/CD8(+) ratio at the TC+IM (p = 0.027), and a higher CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.020). After multivariable analysis, CD8(+) at the TC+IM (p = 0.002), the CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.004), and the number of tumor-positive lymph nodes (p = 0.003) remained significant.
This is the first prospective demonstration of the prognostic utility of immunoprofiling in colon cancer after nodal ultrastaging. Staging based on tumor immunoprofile can augment TNM staging and provide targets for specific immunotherapies.
回顾性数据表明，T细胞标志物的免疫谱分析对结肠癌具有预后价值。对于淋巴结进行超分期的结肠癌患者，前瞻性T细胞免疫谱分析尚未明确。
从一项正在进行的结肠癌淋巴结超分期II期多中心试验的入组患者中选取前瞻性队列。对89例患者的原发性肿瘤标本进行免疫组织化学分析，检测T细胞CD3(+)、CD4(+)、CD8(+)和FOXP3(+)。采用数字图像分析对淋巴细胞群体进行定量。研究结果与5年无病生存率、TNM分期及临床病理变量进行相关性分析。
无病生存期延长与浸润边缘（IM）处较高的CD3(+)计数相关（p = 0.005），与肿瘤中心（TC）和IM处较高的CD8(+)计数相关（p = 0.002），与TC + IM处较低的CD4(+)/CD8(+)比值相关（p = 0.027），与TC + IM处较高的CD8(+)/FOXP3(+)比值相关（p = 0.020）。多变量分析后，TC + IM处的CD8(+)（p = 0.002）、TC + IM处的CD8(+)/FOXP3(+)比值（p = 0.004）以及肿瘤阳性淋巴结数量（p = 0.003）仍具有显著性。
这是首次对结肠癌淋巴结超分期后免疫谱分析的预后价值进行前瞻性论证。基于肿瘤免疫谱的分期可补充TNM分期，并为特定免疫治疗提供靶点。
