Significance of pre-treatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver.
Significance of pre-treatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver.
复制标题
不可切除肝转移结直肠癌患者治疗前免疫学参数的意义。
作者：
J. Zaloudik;L. Lauerová;L. Janakova;R. Talač;M. Šimíčková;M. Nekulová;I. Mikulíková;J. Kovarik;M. Sheard
背景/目的
在这项研究中，我们比较了健康人的外周血淋巴细胞（PBL）亚群和血清细胞因子水平的配置文件与不可切除的肝转移结直肠癌患者开始区域化学免疫治疗前。由于治疗反应仅限于一个子集的患者，我们假设，免疫的初始状态和个体对肿瘤的免疫反应可能是显着的治疗结果。
方法
比较了10例结直肠癌肝转移患者和5例健康人的细胞和体液免疫指标。分析包括外周血单个核细胞的流式细胞术免疫表型（CD 3、CD 4、CD 8、CD 19、CD 25、CD 28、CD 56、CD 57、CD 80和HLA.DR），估计白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF α）的血清细胞因子水平，肿瘤坏死因子-α（TNF-α），和其他免疫学参数是可溶性IL-2受体（sIL-2）、癌胚抗原（CEA）、胃肠癌相关抗原（CA 19-9）和C反应性急性期蛋白（CRP）。与健康对照组相比，在肝定向化疗前，结直肠癌患者中检测到CD 8淋巴细胞的比例显著降低，CD 19，CD 28和CD 80呈下降趋势。
结果
癌症患者表现出显著增加的外周NK细胞群体，如通过CD 56+和CD 57+表型检测到的。与对照组相比，癌症患者的CRP、IL-4和TNF-α、sIL-2 R的血清水平升高，但IL-2未升高。活化的CD 25+淋巴细胞与CD 28+淋巴细胞呈负相关（r =-0.68，p < 0.01），与CD 4+淋巴细胞的相关性较弱（r =-0.56，p < 0.05）。血清IL-4对CD 8+细胞毒性细胞亚群有负性影响（r =-0.57，p < 0.05）。在治疗过程中，疾病进展患者血清sIL-2 R水平与CRP水平呈正相关（r =-0.78，p = 0.01），与TNF-α水平呈正相关（r = 0.64，p = 0.05），CD 4+、CD 19+、CD 28+淋巴细胞初始比例明显低于治疗有效者。在体液参数中，只有sIL-2 R显示与治疗反应的边缘相关性，在无反应患者中升高更多。CEA和CA 19-9的治疗前血清水平显示出与治疗反应和所分析的任何细胞或体液免疫学参数均不相关。
结论
这些结果可以作为一个初步的指导方针，就这样一组测试的基本原理展开讨论，希望能导致标准化的实验室预选和监测区域化疗免疫治疗的患者。
BACKGROUND/AIMS
In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy individuals with those of patients with unresectable liver metastases from colorectal carcinoma before starting regional chemoimmunotherapy. Since the therapeutic responses are limited only to a subset of patients, we hypothesize that the initial status of immunity and individual immune response to a tumor might be significant to the therapeutic outcome.
METHODOLOGY
Cellular and humoral immunological parameters were compared between 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intra-arterial chemo-immunotherapy, and 5 healty individuals. Analyses included a flow cytometric immunophenotyping of peripheral blood mononuclear cells (CD3, CD4, CD8, CD19, CD25, CD28, CD56, CD57, CD80 and HLA.DR), estimation of serum cytokine levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other immunological parameters are soluble IL-2 receptor (sIL-2), carcinoembryonic antigen (CEA), gastrointestinal cancer-associated antigen (CA 19-9), and C-reactive acute phase protein (CRP). A significantly lower proportion of CD8 lymphocytes and a trend for decreased CD19, CD28 and CD80 was detected among colorectal cancer patients before liver-directed chemotherapy compared to healthy controls.
RESULTS
The cancer patients showed a significantly increased population of peripheral NK cells as detected by both CD56+ and CD57+ phenotypes. Elevated serum levels of CRP, IL-4 and TNF-alpha, sIL-2R, but not IL-2, were also demonstrated in cancer patients as compared to controls. Activated CD25+ lymphocytes correlated negatively with CD28+ lymphocytes (r = -0.68, p < 0.01) and less significantly with CD4+ lymphocytes (r = -0.56, p < 0.05). The CD8+ cytotoxic cell subset might be negatively influenced by serum IL-4 (r = -0.57, p < 0.05). Positive correlation was found between sIL-2R and CRP (r = -0.78, p < 0.01), and between sIL-2R and TNF-alpha (r = 0.64, p < 0.05) serum levels in patients with progressive disease during the course of therapy, the initial proportions of CD4+, CD19+ and CD28+ lymphocytes were significantly lower than those among responders. Among humoral parameters, only sIL-2R showed a marginal correlation with therapeutic response, being more elevated among non-responding patients. Pre-treatment serum levels of CEA and CA 19-9 showed correlation with neither therapeutic response nor with any of the cellular or humoral immunological parameters analyzed.
CONCLUSIONS
The results may serve as an initial guideline to open a discussion on the rationale of such a panel of tests, hopefully leading to standardized laboratory pre-selection and monitoring of patients treated with regional chemoimmunotherapy.