[Effects of auto-tumor infiltrating lymphocytes induced by interleukin (IL)-12 with IL-2 on patients of primary hepatic carcinoma].

Abstract

OBJECTIVE:

To investigate the effects of the tumor infiltrating lymphocytes (TILs) from primary hepatic carcinoma (PHC) induced by interleukin-12 (IL-12) with IL-2, on their cytotoxicity, proliferation, and cytokine production, and the immunological function and survival of the PHC patients.

METHODS:

PHC cells and TILs were isolated from the resected tumors and cultured. IL-2 was added into the culture medium with or without IL-12. Ten to 14 days later the cytotoxic activity and proliferation index (PI) of the TILs were calculated. The levels of the cytokine interferon (IFR)-gamma and tumor necrosis factor (TNF)-alpha in the supernatant were tested by ELISA. 20-25 days after the operation the TILs were re-infused into the bodies. The clinical manifestation, cytotoxicity of TILs, phenotype of peripheral blood lymphocytes, and survival of patients were observed.

RESULTS:

1. The cytotoxicity of the TILs of the IL-12 + IL-2 group against the autologous hepatic carcinoma cells was greater than that of the TILs of the IL-2 group (P < 0.05). 2. The PI of the TILs of the IL-12 + IL-2 group was 17.78%, significantly higher than that of the IL-2 group (10.9%, P < 0. 05). 3. The levels of IFN-gamma and TNF-alpha of the IL-12 + IL-2 group were (2180 +/- 494) pg/ml and(485 +/- 98) pg/ml, both significantly higher than those of the IL-2 group [(1078 +/- 309.46) pg/ml and (422.00 +/- 15.81) pg/ml, both P < 0. 05]. 4. After re-infusion of TILs, the CD3+, CD8+, CD4+, and CD56+ rates, especially the CD3+ and CD8+ rates, of the IL-12 + IL-2 group were all significantly higher than those of the IL-2 group (all P < 0.05). 5. After TIL re-infusion the clinical manifestation of all patients were improved. 6. 23 of the 25 patients receiving the re-infusion of the TILs of the IL-12 + IL-2 group survived for more than 1 year, with a rate significantly higher than that of the IL-2 group (17/25, chi2 = 4.5, P < 0.05), however, there were no significant differences in the 3-year and 5-year survival rates between these 2 groups (both P > 0.05). The number of patients who showed recurrence in less than 1 year was 17 in the IL-2 group, with a rate significantly higher that of the IL-12 + IL-2 group (8/25, chi2 = 4.32, P < 0.0 5). However, there was no significant difference in the recurrence rate < or = 3 years between these 2 groups (chi2 = 1.56, P > 0.05).

CONCLUSION:

TILs from primary hepatic carcinoma induced by IL-12 can obviously enhance specific cytotoxicity and proliferation of TILs. TILs induced by IL-12 + IL-2 increase the patients' immunological function, prolong the 1-year survival, and decreases recurrence more effectively than the TILs induced by IL-2 only.

• Authors: Yi-Xin Zhang, Xiao-Ying Wang, Ji-Bin Liu, Su-Qing Zhang, Yi-Ren Chen
• Journal: Zhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 88 Issue 14 Pg. 973-6 (Apr 08 2008) ISSN: 0376-2491 [Print] China
• PMID: 18756970 (Publication Type: English Abstract, Journal Article, Randomized Controlled Trial)

Chemical References

• Interleukin-2
• Interleukin-12

Topics

• Adult
• Aged
• Carcinoma, Hepatocellular (immunology, pathology, therapy)
• Cell Proliferation (drug effects)
• Cytotoxicity, Immunologic (drug effects)
• Follow-Up Studies
• Humans
• Immunotherapy, Adoptive
• Interleukin-12 (pharmacology, therapeutic use)
• Interleukin-2 (pharmacology, therapeutic use)
• Liver Neoplasms (immunology, pathology, therapy)
• Lymphocytes, Tumor-Infiltrating (drug effects, immunology, pathology)
• Middle Aged
• Postoperative Care
• Postoperative Period
• Survival Analysis