Whole blood interferon-γ levels predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer.

Abstract

A core challenge in administering immune-based treatments for cancer is the establishment of easily accessible immunological assays that can predict patients' clinical responses to immunotherapy. In this study, our aim was to predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer. To do this, we evaluated whole blood cytokine levels and peripheral regulatory T cells (Tregs) in 46 patients with unresectable or recurrent pancreatic cancer who received adoptive T-cell therapy at 2-week intervals. To test immune function, venous blood was obtained from patients before the start of therapy and 2 weeks after the 4th treatment. Whole blood interferon (IFN)-α levels (after stimulation with the Sendai virus) were evaluated, as well as the levels of 9 cytokines stimulated with phytohemagglutinin [interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, tumor necrosis factor-α, IFN-γ, and granulocyte-monocyte colony-stimulating factor]. Peripheral Tregs were analyzed by flow cytometry. Using the obtained data, we then observed the relationship between these immunological parameters and clinical outcome of patients. We found that the whole blood production of IFN-γ, IL-2, IL-4, IL-5 and IL-13 significantly increased after adoptive T-cell therapy, whereas the number of peripheral Tregs did not change. Multivariate Cox proportional hazards analyses indicated that the number of peripheral Tregs before receiving adoptive T-cell therapy and the change in IFN-γ levels after adoptive T-cell therapy were independent variables predicting overall survival. The findings of this study indicate that the assay of whole blood IFN-γ production offers promise for evaluating the clinical response of patients to cancer immunotherapy.

• Authors: Takeshi Ishikawa, Satoshi Kokura, Naoyuki Sakamoto, Tetsuya Okayama, Masahiro Endo, Reiko Tsuchiya, Manabu Okajima, Tatsuzo Matsuyama, Satoko Adachi, Kazuhiro Kamada, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Takashi Ando, Kazuko Uno, Yuji Naito, Toshikazu Yoshikawa
• Journal: International journal of cancer (Int J Cancer) Vol. 133 Issue 5 Pg. 1119-25 (Sep 01 2013) ISSN: 1097-0215 [Electronic] United States
• PMID: 23420507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 UICC.

Chemical References

• Cytokines
• Interferon-gamma

Topics

• Adult
• Aged
• Aged, 80 and over
• Cytokines (blood)
• Female
• Humans
• Immunotherapy, Adoptive
• Interferon-gamma (blood)
• Male
• Middle Aged
• Pancreatic Neoplasms (immunology, mortality, therapy)
• Proportional Hazards Models
• T-Lymphocytes (immunology)