PMID- 23785046
OWN - NLM
STAT- MEDLINE
DCOM- 20140205
LR  - 20211119
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 19
IP  - 14
DP  - 2013 Jul 15
TI  - TH2 cytokines from malignant cells suppress TH1 responses and enforce a global 
      TH2 bias in leukemic cutaneous T-cell lymphoma.
PG  - 3755-63
LID - 10.1158/1078-0432.CCR-12-3488 [doi]
AB  - PURPOSE: In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells 
      accumulate in the blood and give rise to widespread skin inflammation. Patients 
      have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper 
      (TH)-1 responses, and most die from infection. Depleting malignant T cells while 
      preserving normal immunity is a clinical challenge. L-CTCL has been variably 
      described as a malignancy of regulatory, TH2 and TH17 cells. EXPERIMENTAL DESIGN: 
      We analyzed phenotype and cytokine production in malignant and benign L-CTCL T 
      cells, characterized the effects of malignant T cells on healthy T cells, and 
      studied the immunomodulatory effects of treatment modalities in patients with 
      L-CTCL. RESULTS: Twelve out of 12 patients with L-CTCL overproduced TH2 
      cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a 
      global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from 
      the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture 
      had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T 
      cells reduced IFNgamma production and neutralizing antibodies to interleukin (IL)-4 
      and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were 
      observed following a variety of treatment modalities that reduced malignant 
      T-cell burden. CONCLUSIONS: A global TH2 bias exists in both benign and malignant 
      T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 
      cytokines from malignant cells strongly inhibited TH1 responses. Our results 
      suggest that therapies that inhibit TH2 cytokine activity, by virtue of their 
      ability to improve TH1 responses, may have the potential to enhance both 
      anticancer and antipathogen responses.
FAU - Guenova, Emmanuella
AU  - Guenova E
AD  - Department of Dermatology, Brigham and Women's Hospital and Harvard Medical 
      School, Boston, Massachusetts 02115, USA.
FAU - Watanabe, Rei
AU  - Watanabe R
FAU - Teague, Jessica E
AU  - Teague JE
FAU - Desimone, Jennifer A
AU  - Desimone JA
FAU - Jiang, Ying
AU  - Jiang Y
FAU - Dowlatshahi, Mitra
AU  - Dowlatshahi M
FAU - Schlapbach, Christoph
AU  - Schlapbach C
FAU - Schaekel, Knut
AU  - Schaekel K
FAU - Rook, Alain H
AU  - Rook AH
FAU - Tawa, Marianne
AU  - Tawa M
FAU - Fisher, David C
AU  - Fisher DC
FAU - Kupper, Thomas S
AU  - Kupper TS
FAU - Clark, Rachael A
AU  - Clark RA
LA  - eng
GR  - R01 AI097128/AI/NIAID NIH HHS/United States
GR  - T32 AR007098/AR/NIAMS NIH HHS/United States
GR  - P50 CA093683/CA/NCI NIH HHS/United States
GR  - P30 AR042689/AR/NIAMS NIH HHS/United States
GR  - R01 CA122569/CA/NCI NIH HHS/United States
GR  - R01 AR063962/AR/NIAMS NIH HHS/United States
GR  - R01 AR056720/AR/NIAMS NIH HHS/United States
GR  - CA9368305/CA/NCI NIH HHS/United States
GR  - R03 MH095529/MH/NIMH NIH HHS/United States
GR  - R01 A1025082/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130619
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (IL13 protein, human)
RN  - 0 (IL4 protein, human)
RN  - 0 (Interleukin-13)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Coculture Techniques
MH  - Female
MH  - Humans
MH  - Interleukin-13/*physiology
MH  - Interleukin-4/*physiology
MH  - Lymphoma, T-Cell, Cutaneous/*immunology/pathology
MH  - Male
MH  - Middle Aged
MH  - Skin Neoplasms/*immunology/pathology
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/*metabolism
MH  - Tumor Burden
MH  - Tumor Cells, Cultured
PMC - PMC3715586
MID - NIHMS475438
EDAT- 2013/06/21 06:00
MHDA- 2014/02/06 06:00
PMCR- 2014/07/15
CRDT- 2013/06/21 06:00
PHST- 2013/06/21 06:00 [entrez]
PHST- 2013/06/21 06:00 [pubmed]
PHST- 2014/02/06 06:00 [medline]
PHST- 2014/07/15 00:00 [pmc-release]
AID - 1078-0432.CCR-12-3488 [pii]
AID - 10.1158/1078-0432.CCR-12-3488 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2013 Jul 15;19(14):3755-63. doi: 10.1158/1078-0432.CCR-12-3488. 
      Epub 2013 Jun 19.