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.

Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis / GARDINI A; ERCOLANI, GIORGIO; RICCOBON A; RAVAIOLI, MATTEO; RIDOLFI L; FLAMINI E; RIDOLFI R; GRAZI, GIAN LUCA; CAVALLARI, ANTONINO; AMADORI D.. - In: JOURNAL OF SURGICAL ONCOLOGY. - ISSN 0022-4790. - STAMPA. - 87:(2004), pp. 46-52. [10.1002/jso.20066]

Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis

GRAZI, GIAN LUCA;
2004

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.
2004
87
46
52
GARDINI A; ERCOLANI, GIORGIO; RICCOBON A; RAVAIOLI, MATTEO; RIDOLFI L; FLAMINI E; RIDOLFI R; GRAZI, GIAN LUCA; CAVALLARI, ANTONINO; AMADORI D....espandi
File in questo prodotto:
File Dimensione Formato  
2004 (J Surg Oncol) Gardini - TIL.pdf

Accesso chiuso

Dimensione 96.4 kB
Formato Adobe PDF
96.4 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1301255
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 38
social impact