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Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin‐2 after radical hepatic resection for colorectal liver metastases: 5‐year analysis
Author(s) -
Gardini Andrea,
Ercolani Giorgio,
Riccobon Angela,
Ravaioli Matteo,
Ridolfi Laura,
Flamini Emanuela,
Ridolfi Ruggero,
Grazi Gian Luca,
Cavallari Antonino,
Amadori Dino
Publication year - 2004
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20066
Subject(s) - medicine , immunotherapy , colorectal cancer , t cell receptor , tumor infiltrating lymphocytes , chemotherapy , interleukin 2 , adjuvant , gastroenterology , immunostaining , cancer , t cell , oncology , immunology , cytokine , immune system , immunohistochemistry
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, 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 ζ‐chain expression significantly increased ( P = 0.001); An increase in TCR ε‐chain expression ( P = 0.04), and p56 lck ( 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 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. J. Surg. Oncol. 2004;87:46–52. © 2004 Wiley‐Liss, Inc.