Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma

Br J Cancer. 2015 Mar 17;112(6):1027-36. doi: 10.1038/bjc.2015.72.

Abstract

Background: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes.

Methods: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method.

Results: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy.

Conclusions: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.

Publication types

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

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • CTLA-4 Antigen / immunology
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Immunophenotyping
  • Interferon-alpha / administration & dosage
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Prognosis
  • Radioimmunotherapy

Substances

  • CD3 Complex
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Interferon-alpha
  • Interleukin-2
  • Interleukin-10
  • Fluorouracil