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               ·310 ·                          南   京 医 科       大 学      学 报                        2024年3月


                    A           Spleen:P13        B         Spleen:Q2⁃UR        C           Spleen:P8
                         10 6                         100                           100
                            Q2⁃UL      Q2⁃UR
                          5 (2.43%)  (1.20%)          ( ×10 4 )                     ( ×10 4 )
                         10
                                1.20%                            P8(35.17%)                    P9(48.00%)
                        Foxp3  10 4                   SSC⁃A  50                     SSC⁃A  50

                         10 3
                            Q2⁃LL      Q2⁃LR
                           (78.17%) (18.20%)
                          0                             0                             0
                                                                                            1
                                                                                              2
                                                                                                   4
                                                                  3
                                                                                                      5
                                                                      5
                                                                    4
                                                                        6
                                                                                                 3
                                                             1
                                                                2
                                1
                                     3
                                        4
                                          5
                                   2
                           0   10 10 10 10 10 10 6       0  10 10 10 10 10 10 10 7     0  10 10 10 10 10 10 6
                                   CD4                          CCR8                          PD⁃1
                    D                             E                             F
                                Spleen:P8             100     Spleen:P8             100     Spleen:P8
                        100
                        ( ×10 4 )   P9(26.19%)        ( ×10 4 )  P9(11.30%)         ( ×10 4 )  P9(16.39%)
                        SSC⁃A  50                     SSC⁃A  50                     SSC⁃A  50
                          0                             0                             0
                                1  2  3  4  5  6              1  2  3  4  5  6              1  2  3  4  5  6
                           0   10 10 10 10 10 10         0   10 10 10 10 10 10         0  10 10 10 10 10 10
                                 CTLA⁃4                         LAG⁃3                         ICOS
                                                                                    +
                         +
                                          +
                             +
                                                       +
                                                                                                 +
                                                                      +
                    A:CD4 Foxp3 Treg cells;B:CCR8 Treg cells;C:PD⁃1 Treg cells;D:CTLA⁃4 Treg cells;E:LAG⁃3 Treg cells;F:ICOS Treg cells.
                                                          +
                                        图7 小鼠脾脏中CCR8 Treg细胞比例与表型流式检测图
                    Figure 7 Proportion and phenotype of CCR8 Treg cells in mouse spleens detected by flow cytometry analysis
                                                        +
                                    A                           B
                                                  CCR8                        PD⁃1
                                                **                          **
                                        ( % )  100    ***          ( % )  100    ***
                                         80
                                        Treg/Treg  60              Treg  60
                                                                    80
                                         40
                                                                    40
                                        CCR8 +  20 0               PD⁃1 + /CCR8 +  20 0
                                           spleen  tumor              spleen  tumor
                                                  peripheral blood           peripheral blood
                       C                          D                          E
                                    CTLA⁃4                      LAG⁃3                      ICOS
                          ( % )    *    ***          ( % )  100  ***  ***       ( % )  100  ***  **
                          Treg 100                   Treg  80                   Treg  80
                           80
                          CTLA⁃4 + /CCR8 +  40       LAG⁃3 + /CCR8 +  40        ICOS + /CCR8 +  40
                                                      60
                           60
                                                                                  60
                           20
                                                                                  20
                                                      20
                            0
                              spleen  tumor            0  spleen  tumor           0  spleen  tumor
                                    peripheral blood            peripheral blood           peripheral blood
                                                 +
                 A:Analysis of the differential proportion of CCR8 subgroups in Tregs in mouse tumor tissues,spleens and peripheral blood. B:Analysis of the dif⁃
                                             +
                                +
              ferential proportion of PD⁃1 subgroups on CCR8 Tregs in mouse tumor tissues,spleens and peripheral blood. C:Analysis of the differential proportion
                                                                                                           +
                                   +
                     +
              of CTLA⁃4 subgroups on CCR8 Tregs in mouse tumor tissues,spleens and peripheral blood. D:Analysis of the differential proportion of LAG⁃3 sub⁃
                                                                                                +
                         +
              groups on CCR8 Tregs in mouse tumor tissues,spleens and peripheral blood. E:Analysis of the differential proportion of ICOS subgroups on CCR8  +
                                                                 ***
                                                          **
                                                   *
              Tregs in mouse tumor tissues,spleen and peripheral blood,P < 0.05,P < 0.01, P < 0.001(n=8).
                                         图8 小鼠肿瘤组织、脾脏、外周血中Treg细胞表型分析
                        Figure 8 The phenotype analysis of Treg cells in mouse tumor tissues,spleens and peripheral blood
              疗方法不断改进,但是卵巢癌患者的生存率并没有                            力。TME 的复杂性和多样性对免疫治疗的效果具
              明显提高。近年来免疫治疗逐渐显示出巨大潜                              有重要影响。深入阐明卵巢癌免疫抑制微环境的
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