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World J Gastroenterol. 2015 Oct 21;21(39):11168-78. doi: 10.3748/wjg.v21.i39.11168.

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

Author information

  • 1Shintaro Tsukinaga, Mikio Kajihara, Kazuki Takakura, Zensho Ito, Tomoya Kanai, Keisuke Saito, Shinichiro Takami, Hiroko Kobayashi, Yoshihiro Matsumoto, Shunichi Odahara, Kan Uchiyama, Toshifumi Ohkusa, Shigeo Koido, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa City, Chiba 277-8567, Japan.

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.

KEYWORDS:

Chemoimmunotherapy; Delayed-type hypersensitivity; Dendritic cell; Interleukin-6; Interleukin-8; Pancreatic cancer; Wilms’ tumor 1

PMID:
26494971
PMCID:
PMC4607914
DOI:
10.3748/wjg.v21.i39.11168
[PubMed - indexed for MEDLINE]
Free PMC Article
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