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EnglishBACKGROUND AND OBJECTIVES: Conventional chemotherapy has not proven effective in improving long-term results of surgery for liver metastases from colorectal cancer. We assessed the usefulness of immunotherapy with tumor infiltrating lymphocytes (TIL) plus Interleukin-2 (IL-2) as adjuvant treatment. METHODS: Between 1995 and 1998, 47 patients were enrolled onto a prospective protocol; 25 entered the treatment group (A) and 22 entered the control group (B). All patients had undergone radical liver resection. TIL obtained from surgical specimens from group A patients were cultured and activated in vitro with IL-2, then reinfused into the patients with IL-2. We investigated pre- and post-IL-2 stimulation expression of T cell receptor (TCR) zeta- and epsilon-chains, p56(lck), Fas, and Fas-L by TIL immunostaining. RESULTS: Fourteen patients from group A (56%) received immunotherapy; 14 from group B (60%) underwent conventional chemotherapy, and the remaining 19 patients did not receive any treatment. No significant differences between the two groups were found in the actuarial and disease-free survival (DSF) rates after 1, 3, and 5 years. After IL-2 exposure, TCR zeta-chain expression significantly increased (P = 0.001); An increase in TCR epsilon-chain expression (P = 0.04), and p56(lck) (P = 0.03) was detected; TCR epsilon-chain expression was significantly increased in disease-free patients compared to those who relapsed (P = 0.04). Fas-L expression was correlated with the TCR epsilon-chain and p56(lck) levels (P = 0.05). CONCLUSIONS: Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells.
| Titolo: | Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis. | |
| Autore/i: | GARDINI A; ERCOLANI, GIORGIO; RICCOBON A; RAVAIOLI, MATTEO; RIDOLFI L; FLAMINI E; RIDOLFI R; GRAZI, GIAN LUCA; CAVALLARI, ANTONINO; AMADORI D. | |
| Autore/i Unibo: | ||
| Anno: | 2004 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1002/jso.20066 | |
| Abstract: | BACKGROUND AND OBJECTIVES: Conventional chemotherapy has not proven effective in improving long-term results of surgery for liver metastases from colorectal cancer. We assessed the usefulness of immunotherapy with tumor infiltrating lymphocytes (TIL) plus Interleukin-2 (IL-2) as adjuvant treatment. METHODS: Between 1995 and 1998, 47 patients were enrolled onto a prospective protocol; 25 entered the treatment group (A) and 22 entered the control group (B). All patients had undergone radical liver resection. TIL obtained from surgical specimens from group A patients were cultured and activated in vitro with IL-2, then reinfused into the patients with IL-2. We investigated pre- and post-IL-2 stimulation expression of T cell receptor (TCR) zeta- and epsilon-chains, p56(lck), Fas, and Fas-L by TIL immunostaining. RESULTS: Fourteen patients from group A (56%) received immunotherapy; 14 from group B (60%) underwent conventional chemotherapy, and the remaining 19 patients did not receive any treatment. No significant differences between the two groups were found in the actuarial and disease-free survival (DSF) rates after 1, 3, and 5 years. After IL-2 exposure, TCR zeta-chain expression significantly increased (P = 0.001); An increase in TCR epsilon-chain expression (P = 0.04), and p56(lck) (P = 0.03) was detected; TCR epsilon-chain expression was significantly increased in disease-free patients compared to those who relapsed (P = 0.04). Fas-L expression was correlated with the TCR epsilon-chain and p56(lck) levels (P = 0.05). CONCLUSIONS: Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells. | |
| Data prodotto definitivo in UGOV: | 2005-10-10 | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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