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目的探讨C127细胞全细胞性抗原致敏的DC激活的TIL体外抗小鼠乳腺癌活性,并将C127细胞全细胞性抗原致敏的DC激活的TIL(C127-DC-TIL)过继免疫荷瘤小鼠,研究其对C127荷瘤小鼠免疫功能的影响及抑瘤作用。方法从小鼠四肢长骨骨髓中获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白介素-4(IL-4)和肿瘤全细胞性抗原致敏DC,然后用DC激活TIL,观察TIL在体外对C127细胞、MA782细胞和B16细胞的杀伤活性;检测应用C127-DC-TIL后荷瘤小鼠的脾淋巴细胞的NK、LAK、CTL活性、血清TNF活性、抑瘤作用以及瘤体病理改变,并与对照组相比较。结果①C127-DC-TIL具有很强的对C127细胞杀伤活性[杀伤率为(70.21±2.86)%],明显高于其对MA782和B16细胞的杀伤活性[杀伤率分别为(51.31±3.25)%,(31.41±2.65)%],也明显高于未经DC激活的TIL、C127-DC-脾淋巴细胞和未经DC激活的脾淋巴细胞对C127细胞杀伤活性[杀伤率分别为(48.30±2.97)%,(47.76±3.43)%和(17.23±2.56)%]和对MA782细胞杀伤活性[杀伤率分别为(38.52±2.87)%,(36.62±2.75)%和(18.07±2.40)%]以及对B16细胞杀伤活性[杀伤率分别为(25.38±2.63)%,(24.82±2.81)%和(17.34±2.81)%],同时B16细胞全细胞性抗原致敏的DC激活的TIL(B16-DC-TIL,TIL来源于C127瘤体)也可诱导相对较低的对B16细胞的特异性细胞杀伤活性。②C127-DC-TIL可明显诱导提高荷瘤小鼠脾淋巴细胞NK、LAK和CTL活性[活性分别为(32.21±1.24)%(、30.35±1.72)%和(37.43±1.54)%],并可检测到血清TNF水平明显上升[血清TNF水平为(38.41±1.77)U/ml],它们均达正常对照组水平,与未经DC激活的TIL组、C127-DC-脾淋巴细胞组、未经DC激活的脾淋巴细胞组、生理盐水组分别对应比较,差异均有显著性(P<0.01)。该组瘤体内淋巴细胞浸润程度也高于对照组,其瘤体生长明显受到抑制。结论①C127-DC-TIL可产生很强的体外针对C127细胞的特异性杀伤活性。②C127-DC-TIL具有很强的特异性抗小鼠乳腺癌作用。
Objective To investigate the anti-mouse mammary tumor activity induced by C127 cell-full-cell antigen-primed DC in vitro and adoptive immunization with C127-cell-primed DCs (C127-DC-TIL) Rats, to study its immune function in C127 tumor-bearing mice and anti-tumor effect. Methods DCs were harvested from the long bone marrow of the limbs of mice. DCs were stimulated with GM-CSF, IL-4 and tumor cell-specific antigens. TIL was then activated by DCs. TIL in vitro on C127 cells, MA782 cells and B16 cells; detection of C127-DC-TIL tumor-bearing mice after spleen lymphocytes NK, LAK, CTL activity, serum TNF activity, tumor suppression and tumor Pathological changes, and compared with the control group. Results ①C127-DC-TIL had a strong cytotoxic activity against C127 cells (killing rate was (70.21 ± 2.86)%], which was significantly higher than that of its killing activity on MA782 and B16 cells (killing rates were 51.31 ± 3.25% , (31.41 ± 2.65)%], which was also significantly higher than that of non-DC-activated TIL, C127-DC-splenic lymphocytes and non-DC-activated splenic lymphocytes. The killing rates of C127 cells were (48.30 ± 2.97 ), (47.76 ± 3.43)% and (17.23 ± 2.56)%, respectively) and cytotoxic activity against MA782 cells (38.52 ± 2.87%, 36.06 ± 2.75% and 18.07 ± 2.40%, respectively) The killing activity of B16 cells (25.38 ± 2.63%, (24.82 ± 2.81)% and (17.34 ± 2.81)%], respectively, while B16-cell-fully antigenic DC activated TIL -TIL, TIL derived from C127 tumor) can also induce a relatively low specific cytotoxic activity on B16 cells. ② The activity of NK, LAK and CTL in splenic lymphocytes of tumor-bearing mice [(32.21 ± 1.24)% (30.35 ± 1.72)% and (37.43 ± 1.54)%] were significantly increased by C127-DC-TIL, Serum TNF levels were significantly increased (serum TNF levels were (38.41 ± 1.77) U / ml], they reached the level of the normal control group, with non-activated TIL group, C127-DC-splenic lymphocyte group, without DC activated splenic lymphocyte group and saline group respectively, the difference was significant (P <0.01). The tumor in vivo lymphocyte infiltration is also higher than the control group, the tumor growth was significantly inhibited. Conclusion ①C127-DC-TIL can produce strong cytotoxic activity against C127 cells in vitro. ② C127-DC-TIL has a strong specific anti-mouse breast cancer effect.