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

被引:49
作者
Karakhanova, S. [1 ]
Ryschich, E. [1 ]
Mosl, B. [1 ]
Harig, S. [1 ,2 ]
Jaeger, D. [2 ]
Schmidt, J. [1 ,3 ]
Hartwig, W. [4 ]
Werner, J. [4 ]
Bazhin, A. V. [1 ,4 ]
机构
[1] Univ Heidelberg Hosp, Dept Gen Surg, D-69120 Heidelberg, Germany
[2] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany
[3] Gen & Visceral Surg Ctr, CH-8002 Zurich, Switzerland
[4] Hosp Univ Munich, Dept Gen Visceral Transplantat Vasc & Thorac Surg, D-81377 Munich, Germany
关键词
immunotherapy; interferon-alpha; CapRI; pancreatic carcinoma; overall survival; disease-free survival; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; ADJUVANT CHEMOTHERAPY; INTERFERON-ALPHA; FOLINIC ACID; IN-VITRO; T-CELLS; CANCER; GEMCITABINE; IMMUNOTHERAPY;
D O I
10.1038/bjc.2015.72
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-alpha 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.
引用
收藏
页码:1027 / 1036
页数:10
相关论文
共 38 条
[1]   Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers [J].
Badoual, C ;
Hans, S ;
Rodriguez, J ;
Peyrard, S ;
Klein, C ;
Agueznay, NE ;
Mosseri, V ;
Laccourreye, O ;
Bruneval, P ;
Fridman, WH ;
Brasnu, DF ;
Tartour, E .
CLINICAL CANCER RESEARCH, 2006, 12 (02) :465-472
[2]   Clinical model:: Interferons activate human monocytes to an eradicative tumor cell level in vitro [J].
Baron, Samuel ;
Hernandez, Jessica ;
Bekisz, Joseph ;
Poast, Joyce ;
Goldman, Neil ;
Clouse, Kathleen ;
Fields, Karen ;
Bacot, Sylvia ;
Wang, Jiun ;
Zoon, Kathryn .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2007, 27 (02) :157-163
[3]   Near Eradication of Clinically Relevant Concentrations of Human Tumor Cells by Interferon-Activated Monocytes In Vitro [J].
Baron, Samuel ;
Finbloom, Joel ;
Horowitz, Julie ;
Bekisz, Joseph ;
Morrow, Angel ;
Zhao, Tongmao ;
Fey, Samuel ;
Schmeisser, Hana ;
Balinsky, Corey ;
Miyake, Kotaro ;
Clark, Christopher ;
Zoon, Kathryn .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2011, 31 (07) :569-573
[4]   Overcoming immunosuppression as a new immunotherapeutic approach against pancreatic cancer [J].
Bazhin, Alexandr V. ;
Bayry, Jagadeesh ;
Umansky, Viktor ;
Werner, Jens ;
Karakhanova, Svetlana .
ONCOIMMUNOLOGY, 2013, 2 (09)
[5]   Two immune faces of pancreatic adenocarcinoma: possible implication for immunotherapy [J].
Bazhin, Alexandr V. ;
Shevchenko, Ivan ;
Umansky, Viktor ;
Werner, Jens ;
Karakhanova, Svetlana .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2014, 63 (01) :59-65
[6]   Immunology of Gynecologic Neoplasms: Analysis of the Prognostic Significance of the Immune Status [J].
Bellati, F. ;
Visconti, V. ;
Napoletano, C. ;
Antonilli, M. ;
Frati, L. ;
Panici, P. Benedetti ;
Nuti, M. .
CURRENT CANCER DRUG TARGETS, 2009, 9 (04) :541-565
[7]   A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma [J].
Chan, Stephen L. ;
Mo, Frankie K. F. ;
Wong, Cesar S. C. ;
Chan, Charles M. L. ;
Leung, Linda K. S. ;
Hui, Edwin P. ;
Ma, Brigette B. ;
Chan, Anthony T. C. ;
Mok, Tony S. K. ;
Yeo, Winnie .
CANCER, 2012, 118 (16) :3984-3992
[8]   FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer [J].
Conroy, Thierry ;
Desseigne, Francoise ;
Ychou, Marc ;
Bouche, Olivier ;
Guimbaud, Rosine ;
Becouarn, Yves ;
Adenis, Antoine ;
Raoul, Jean-Luc ;
Gourgou-Bourgade, Sophie ;
de la Fouchardiere, Christelle ;
Bennouna, Jaafar ;
Bachet, Jean-Baptiste ;
Khemissa-Akouz, Faiza ;
Pere-Verge, Denis ;
Delbaldo, Catherine ;
Assenat, Eric ;
Chauffert, Bruno ;
Michel, Pierre ;
Montoto-Grillot, Christine ;
Ducreux, Michel .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (19) :1817-1825
[9]   Biomarkers for the development of cancer vaccines - Current status [J].
Copier, John ;
Whelan, Mike ;
Dalgleish, Angus .
MOLECULAR DIAGNOSIS & THERAPY, 2006, 10 (06) :337-343
[10]   Survival among patients with adenocarcinoma of the pancreas: A population-based study (United States) [J].
Cress, RD ;
Yin, DX ;
Clarke, L ;
Bold, R ;
Holly, EA .
CANCER CAUSES & CONTROL, 2006, 17 (04) :403-409