目的:揭示紫杉醇联合卡铂对荷瘤大鼠免疫系统的影响,探讨化疗后是否存在免疫功能逆转的“窗口期”。方法:取25只Fischer 344大鼠,随机分为5组,取4组于右腋下种植NuTu-19卵巢癌细胞株,待荷瘤体积生长至0.5cm3后,以牺牲大鼠的时间为第0天,取3组分别于-15天(化疗晚期)、-10天(化疗中期)、-6天(化疗早期)在荷瘤的大鼠腹腔内注射紫杉醇、卡铂。流式细胞技术检测化疗后各时期淋巴细胞数量及刺激活化后外周血Tc1淋巴细胞的功能亚群,H3-TdR掺入法检测化疗后淋巴细胞的增殖。结果:荷瘤鼠与正常大鼠相比,淋巴细胞数量无显著差异,荷瘤组淋巴细胞亚群CD3+T、CD4+T、CD8+T、NK细胞下降,但仅CD3+T细胞较正常组有差异(P<0.05)。荷瘤组肿瘤抑制性Treg细胞明显增高(P<0.05),而具有杀伤功能的Tc1细胞在荷瘤组明显下降(P<0.05),NK的杀伤功能在两组间无显著差异。移植瘤大鼠化疗后免疫功能变化:(1)在用药后不同阶段淋巴细胞数呈先下降后逐渐恢复至正常的变化规律,在化疗后6天降到最低点,15天恢复至化疗前水平;(2)化疗后6天淋巴细胞降到最低,其增殖力最强;(3)化疗后机体外周血中CD3+T、CD4+T、CD8+T细胞、肿瘤抑制性Treg细胞绝对数均先下降后恢复,化疗后6天降到最低,较未化疗组均有统计学意义,化疗后10天开始恢复,化疗后15天均恢复到化疗前水平;(4)化疗后CD8+T细胞中Tc1细胞比例逐渐增高,化疗后6天较未化疗组增高且有统计学意义,化疗后15天达到最高,但较化疗后6天无显著性差异,表明化疗促进具有杀伤功能Tc1的表达。结论:荷瘤鼠的机体呈负调节免疫状态,肿瘤的发生引起了免疫功能的逃逸,肿瘤的免疫治疗应该具有针对性;紫杉醇联合卡铂打破机体内原有的抗肿瘤免疫抑制状态,机体有可能通过免疫重建诱生了增强的抗肿瘤免疫应答,从而使抗肿瘤免疫抑制状态得到暂时逆转,表明机体经化疗后存在免疫“窗口期”。 OBJECTIVE: To reveal the effect of paclitaxel combined with carboplatin on the immune system in tumor-bearing rats and to explore whether there is a “window period” after immunotherapy. Methods: Twenty-five Fischer 344 rats were randomly divided into 5 groups. NuTu-19 ovarian cancer cell lines were planted in the right axilla of 4 groups. After the tumor volume grew to 0.5 cm3, On days 0 and 3, paclitaxel and carboplatin were intraperitoneally injected in tumor-bearing rats at -15 days (late chemotherapy), -10 days (middle chemotherapy), and -6 days (early chemotherapy). Flow cytometry was used to detect the number of lymphocytes and the functional subsets of Tc1 lymphocytes in peripheral blood after chemotherapy. The proliferation of lymphocytes after chemotherapy was detected by H3-TdR incorporation. Results: There was no significant difference in the number of lymphocytes in tumor-bearing mice compared with normal rats. The number of CD3 + T, CD4 + T, CD8 + T and NK cells in tumor-bearing group was decreased, but only CD3 + T cells were normal Group differences (P <0.05). Tumor suppressor Treg cells in tumor-bearing group were significantly increased (P <0.05), while Tc1 cells with killing function was significantly decreased in tumor-bearing group (P <0.05). NK cytotoxicity was not significantly different between the two groups. The changes of immune function in the transplanted tumor of rats after chemotherapy: (1) The number of lymphocytes gradually decreased to the lowest level at 6 days after chemotherapy, and returned to the level before chemotherapy after 15 days ; (2) lymphocytes were the lowest on the 6th day after chemotherapy, and had the strongest proliferation ability; (3) The absolute number of CD3 + T, CD4 + T, CD8 + T cells and tumor suppressor Treg cells in the peripheral blood of patients after chemotherapy After the first decline, the recovery was restored. The levels of CD8 + T cells decreased after 6 days of chemotherapy, which were significantly lower than those of the non-chemotherapy group. The recovery started 10 days after chemotherapy and returned to the level of pre-chemotherapy 15 days after chemotherapy. (4) The proportion of Tc1 cells increased gradually. Compared with the non-chemotherapy group, the proportion of Tc1 cells increased gradually after 6 days of chemotherapy, reached the highest level 15 days after chemotherapy, but no significant difference compared with 6 days after chemotherapy, indicating that chemotherapy promoted the expression of Tc1 with killing function. Conclusion: The body of tumor-bearing mice showed a negative regulation of immune status, the occurrence of tumors caused immune escape, tumor immunotherapy should be targeted; paclitaxel combined with carboplatin to break the body’s original anti-tumor immunosuppressive state, the body has It is possible to induce an enhanced anti-tumor immune response through immune reconstitution, thereby temporarily reversing the antitumor immunosuppressive state, indicating that there is immunity “window period” after chemotherapy.