Prognostic significance of plasma interleukin-6/-8 in pancreatic cancer patients receiving chemoimmunotherapy.

Abstract

AIM:

To investigate the association of plasma levels of interleukin (IL)-6 and -8 with Wilms' tumor 1 (WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDA) treated with dendritic cells (DCs) pulsed with three types of major histocompatibility complex class I and II-restricted WT1 peptides combined with chemotherapy.

METHODS:

During the entire treatment period, plasma levels of IL-6 and -8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity (DTH) test.

RESULTS:

Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival (OS) was significantly longer in PDA patients with low plasma IL-6 levels (< 2 pg/mL) after 5 vaccinations than in patients with high plasma IL-6 levels (≥ 2 pg/mL) (P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.

CONCLUSION:

Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.

• Authors: Shintaro Tsukinaga, Mikio Kajihara, Kazuki Takakura, Zensho Ito, Tomoya Kanai, Keisuke Saito, Shinichiro Takami, Hiroko Kobayashi, Yoshihiro Matsumoto, Shunichi Odahara, Kan Uchiyama, Hiroshi Arakawa, Masato Okamoto, Haruo Sugiyama, Kazuki Sumiyama, Toshifumi Ohkusa, Shigeo Koido
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 39 Pg. 11168-78 (Oct 21 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 26494971 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• CXCL8 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-8
• Peptide Fragments
• WT1 Proteins
• WT1 protein, human
• Deoxycytidine
• Gemcitabine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects)
• Biomarkers, Tumor (blood)
• Carcinoma, Pancreatic Ductal (blood, drug therapy, immunology, mortality, pathology)
• Cells, Cultured
• Chemotherapy, Adjuvant
• Dendritic Cells (immunology, transplantation)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunologic Tests
• Immunotherapy (adverse effects, methods)
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Pancreatic Neoplasms (blood, drug therapy, immunology, mortality, pathology)
• Peptide Fragments (immunology)
• Time Factors
• Tomography, X-Ray Computed
• Treatment Outcome
• WT1 Proteins (immunology)
• Gemcitabine