Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma.
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.
Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
S
S
Karakhanova
Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
E
E
Ryschich
Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
B
B
Mosl
1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
S
S
Harig
National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
D
D
Jäger
1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] General and Visceral Surgery Center, 8002 Zurich, Switzerland.
J
J
Schmidt
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany.
W
W
Hartwig
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany.
J
J
Werner
1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany.
A V
AV
Bazhin
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D060908:CTLA-4 Antigen / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000008:administration & dosage; D016753:Interleukin-10 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D016499:Radioimmunotherapy
D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016898:Interferon-alpha; D007376:Interleukin-2; D016753:Interleukin-10; D005472:Fluorouracil