PMID- 8386711
OWN - NLM
STAT- MEDLINE
DCOM- 19930525
LR  - 20210102
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 54
IP  - 1
DP  - 1993 Apr 22
TI  - In vitro anti-tumor activity of eosinophils from cancer patients treated with 
      subcutaneous administration of interleukin 2. Role of interleukin 5.
PG  - 8-15
AB  - Interleukin 2 (IL-2) administration is known to induce marked eosinophilia. To 
      evaluate the potential role of eosinophils as anti-tumor effectors and to 
      understand the direct or indirect effects of IL-2 on eosinophils, the physical 
      and functional characteristics of eosinophils obtained during IL-2 therapy were 
      compared with those of eosinophils obtained from the same patients before IL-2 
      administration, or from healthy donors. The treatment schedule consisted of 
      subcutaneous (s.c.) injections of IL-2, and was performed in 7 patients with 
      small-cell lung cancer (SCLC) in advanced stage. A marked increase of hypodense 
      cells in peripheral blood was found to correlate with eosinophil activation in 
      patients undergoing IL-2 therapy. Cytotoxic activity of eosinophils against 
      allogeneic tumor cells (SCLC, K562 and melanoma lines), as assessed by direct and 
      antibody (Ab)-dependent cellular cytotoxicity (ADCC), was markedly increased 
      during IL-2 therapy. Conversely, eosinophils obtained before treatment, like 
      those of healthy donors, lacked any activity against tumor cells. Sera from 
      IL-2-treated, but not from untreated, patients, significantly improved the in 
      vitro survival and anti-tumor cytotoxicity of eosinophils from healthy donors. 
      Comparable effects were obtained with eosinophils cultured with interleukin 5 
      (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF) and, to a 
      lesser extent, by tumor necrosis factor-alpha (TNF alpha), while no direct 
      activity was mediated by IL-2. A 91% inhibition of eosinophil ADCC was found 
      after pre-incubation of the sera of IL-2-treated patients with anti-IL-5 but not 
      with anti-GM-CSF or anti-TNF alpha Ab. IL-5 mRNA expression was detected in 
      peripheral-blood lymphocytes (PBL) obtained 4 hr after IL-2 injection during the 
      second and third week of IL-2 therapy. Phenotypic analysis of eosinophils from 
      IL-2-treated patients showed enhanced expression of activation markers, including 
      Fc gamma RII (CD32), HLA-DR, CR3 (CD11b) and CRI (CD35). These findings suggest 
      that a significant cytotoxicity against tumor cells can be mediated by 
      eosinophils after indirect, IL-5-mediated in vivo activation by IL-2, and that 
      eosinophils may be involved in the anti-tumor response(s) induced in vivo by 
      IL-2.
FAU - Rivoltini, L
AU  - Rivoltini L
AD  - Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
FAU - Viggiano, V
AU  - Viggiano V
FAU - Spinazze, S
AU  - Spinazze S
FAU - Santoro, A
AU  - Santoro A
FAU - Colombo, M P
AU  - Colombo MP
FAU - Takatsu, K
AU  - Takatsu K
FAU - Parmiani, G
AU  - Parmiani G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukin-5)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
EIN - Int J Cancer 1993 Jul 9;54(5):887
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Carcinoma, Small Cell/*drug therapy
MH  - Cytotoxicity, Immunologic
MH  - Eosinophils/*immunology
MH  - Evaluation Studies as Topic
MH  - Gene Expression
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/physiology
MH  - Humans
MH  - Immunity, Cellular
MH  - Interleukin-2/*antagonists & inhibitors
MH  - Interleukin-5/*physiology
MH  - Lung Neoplasms/*drug therapy
MH  - RNA, Messenger/genetics
MH  - Tumor Necrosis Factor-alpha/physiology
EDAT- 1993/04/22 00:00
MHDA- 1993/04/22 00:01
CRDT- 1993/04/22 00:00
PHST- 1993/04/22 00:00 [pubmed]
PHST- 1993/04/22 00:01 [medline]
PHST- 1993/04/22 00:00 [entrez]
AID - 10.1002/ijc.2910540103 [doi]
PST - ppublish
SO  - Int J Cancer. 1993 Apr 22;54(1):8-15. doi: 10.1002/ijc.2910540103.