Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study

Cancer Immunol Immunother. 2012 Oct;61(10):1781-90. doi: 10.1007/s00262-012-1226-4. Epub 2012 Mar 16.


Purpose: To clarify the long-term effect of immunotherapy, the effect of adoptive activated T lymphocyte immunotherapy on advanced lung cancer was evaluated in terms of survival time. In addition, the performance status of cancer patients under immunotherapy was examined.

Experimental design: Over 5 × 10(9) alpha-beta T lymphocytes cultured ex vivo with an immobilized anti-CD3 antibody and interleukin-2 were injected intravenously into patients, once every 2 weeks for 3 months or longer. Follow-up of these patients was carried out using clinical records and by telephone interview questionnaire. Patients undergoing immunotherapy in immunotherapy clinics and those undergoing other anticancer therapies without immunotherapy in seven hospitals in Tokyo were enrolled in this study. Data were analyzed by a third-party statistician. Performance status was studied on another series of various cancer patients who underwent immunotherapy.

Results: The overall median survival time of the patients with the best supportive care, which was obtained using Kaplan-Meier's model, was 5.6 months, and those with immunotherapy alone, chemotherapy alone, and immuno-chemotherapy were 12.5, 15.7, and 20.8 months, respectively. Using Cox' proportional hazard model, we examined the possible factors on survival time by univariate analysis. Then, the patients were stratified by gender and histological type for multivariate analysis. Significantly low hazard ratios were observed for immunotherapy and radiotherapy in males with squamous cancer; for chemotherapy and radiotherapy in male with adenocarcinoma; and for immunotherapy in females with adenocarcinoma. Addition of immunotherapy to chemotherapy resulted in a statistically significant decrease in hazard ratio in females with adenocarcinoma. Studies on the performance status (PS), determined according to the European Cooperative Oncology Group criteria, revealed a continuous high level of PS under immunotherapy until around 2 months before death, in contrast to the gradual increase of tumor marker level.

Conclusions: The effectiveness of immunotherapy on advanced lung cancer is limited but may extend life span under certain conditions. Immunotherapy itself provided no clinical benefit by itself as compared with chemotherapy, but a significant additive effect of immunotherapy on chemotherapy was observed in females with adenocarcinoma. Moreover, immunotherapy can maintain good quality of life of the patients until near the time of death.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / therapy*
  • Adenocarcinoma of Lung
  • Aged
  • Antibodies, Neutralizing / pharmacology
  • CD3 Complex / immunology
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / therapy*
  • Cells, Cultured
  • Cohort Studies
  • Combined Modality Therapy / methods
  • Combined Modality Therapy / statistics & numerical data
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / statistics & numerical data
  • Interleukin-2 / pharmacology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / therapy*
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / transplantation*
  • Treatment Outcome


  • Antibodies, Neutralizing
  • CD3 Complex
  • IL2 protein, human
  • Interleukin-2