Holcombe R F, Jacobson J, Dakhil S R, Stewart R M, Betzing K S, Kannan K, Macdonald J S
Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, Orange, Calif., USA.
Cancer Immunol Immunother. 1999 Dec;48(9):533-9. doi: 10.1007/s002620050602.
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: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4: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 follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA 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 are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.
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5-氟尿嘧啶/左旋咪唑（5FU/LMS）治疗前、治疗期间及治疗12个月后免疫参数的变化是否与无病生存期相关，38例入组西南肿瘤协作组（SWOG）8899方案的患者在治疗前以及治疗开始后3、6、12和15个月接受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。从3个月开始直至15个月，CD56+自然杀伤细胞的比例和总数均显著增加（P<0.001）。治疗期间，表达CD25（白细胞介素-2受体）、VLA4以及CD4:CD45RA和CD4:CDw29组合的细胞总数未见明显增加，但在15个月时出现增加（CD25、CD4:CDw29、CD4:CD45RA，P<0.05；VLA4，P<0.001）。治疗开始前及治疗3个月后CD8+细胞水平较低与5FU/LMS治疗第一年的早期复发相关。无病生存的患者（n=22，中位随访45个月）主要在15个月时，CD8+、CD25+、CD56+、VLA4+、CD4:CDw29和CD4:CD45RA细胞总数增加。相比之下，复发患者的CD8+、CD4:CDw29、CD4:CD45RA和VLA4+细胞数量减少，CD56+和CD25+细胞仅有少量增加。在15个月检测时，晚期复发组与无病生存组之间，CD25+、CD4:CD45RA和CD4:CDw29细胞存在统计学显著差异（分别为P=0.0276、P=0.0349、P=0.0178）。总之，在5FU/LMS治疗期间尤其是治疗结束后，淋巴细胞表型出现多种改变，参与细胞介导免疫反应的细胞比例和总数增加。其中许多变化与临床结局显著相关，可能有助于辅助治疗结束后III期结肠癌患者的风险分层。
