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

• Published in: Journal of surgical oncology 2004-07, Vol.87 (1), p.46-52
• Main Authors: Gardini, Andrea, Ercolani, Giorgio, Riccobon, Angela, Ravaioli, Matteo, Ridolfi, Laura, Flamini, Emanuela, Ridolfi, Ruggero, Grazi, Gian Luca, Cavallari, Antonino, Amadori, Dino
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; adoptive immunotherapy; Adult; Aged; colorectal cancer; Colorectal Neoplasms - pathology; Female; Hepatectomy; Humans; Immunotherapy, Adoptive; Interleukin-2 - therapeutic use; liver metastases; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Liver Neoplasms - therapy; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - biosynthesis; Lymphocytes, Tumor-Infiltrating - transplantation; Male; Membrane Proteins - biosynthesis; Middle Aged; Prospective Studies; Receptors, Antigen, T-Cell - biosynthesis; TIL
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.20066

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) ζ‐ and ε‐chains, p56lck, 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 ζ‐chain expression significantly increased (P = 0.001); An increase in TCR ε‐chain expression (P = 0.04), and p56lck (P = 0.03) was detected; TCR ε‐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 ε‐chain and p56lck 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. J. Surg. Oncol. 2004;87:46–52. © 2004 Wiley‐Liss, Inc.