Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009
Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009
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DOI：
10.1007/s002620050602
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发表时间：
1999-12-01
影响因子：
5.8
通讯作者：
Macdonald, JS
中科院分区：
文献类型：
--
作者：
Holcombe, RF;Jacobson, J;Macdonald, JS
左旋咪唑(LMS)用于III期结肠癌患者的辅助治疗，具有免疫调节作用。为了确定5FU/LMS治疗前、治疗中和治疗12个月后免疫参数的变化是否与无病生存相关，38名参加西南肿瘤小组(SWOG)8899方案的患者在治疗前以及治疗开始后3、6、12和15个月进行了广泛的淋巴细胞表型分析。患者的中位随访时间为41个月，CD56(+)自然杀伤细胞的比例和总数显著增加，从3个月开始一直持续到15个月(P<；0.001)。表达CD25(白介素2受体)、VLA4以及CD4：C3D45RA和CD4：CDw29的细胞总数在治疗期间没有明显增加，但在15个月时出现(P<；0.05)。CD25、CD3：CDw29、CD4：CD45RA；P<；0.001：Vla4)。低水平的CD8(+)细胞在治疗开始前和治疗3个月后与5FU/LMS治疗第一年内的早期复发相关。无病患者(n=22，中位随访45个月)CD8(+)、CD25(+)、CD56(+)、VLA4(+)、CD4：CDw29和CD4：CD45RA细胞总数增加，主要集中在15个月。相比之下，复发患者CD8(+)、CD4：CDw29、CD4：CD35RA和VLA4(+)细胞数量减少，CD56(+)和CD25(+)细胞略有增加。15个月检测时，晚期复发组CD25(+)、CD_4：CD_(45)RA、CD_4：CD_(29)细胞数与未复发组比较差异有统计学意义(P=0.0276，P=0.0349，P=0.0178)。综上所述，在5FU/LMS治疗期间，尤其是在完成5FU/LMS治疗后，淋巴细胞表型发生了多重变化，参与细胞介导的免疫反应的细胞比例和总数增加，其中许多变化与临床结果显著相关，并可能有助于完成辅助治疗后III期结肠癌患者的风险分层。
Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months, Significant increases in the proportion and total number of CD56(+) natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0.001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: C3D45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05. CD25, CD3:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8(+) cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median followup 45 months) demonstrated increases in the total numbers of CD8(+), CD25(+), CD56(+), VLA4(+), CD4: CDw29 and CD4:CD45RA cells, primarily at 15 rrmonths.In contrast, patients who relapsed had decreased numbers of CD8(+), CD4:CDw29, CD4: CD35RA and VLA4(+) cells and minimal increases in CD56(+) and CD25(+) cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25(+), CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS, Many of these changes ars-significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.