The cytokine microenvironment of human colon carcinoma. Lymphocyte expression of tumor necrosis factor-alpha and interleukin-4 predicts improved survival.
Cancer
; 78(6): 1168-78, 1996 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-8826937
ABSTRACT
BACKGROUND:
The functional significance of cytokines expressed in situ by tumor cells and tumor infiltrating lymphocytes (TIL) in human colon carcinomas is largely unknown.METHODS:
We assessed TIL expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), granulocyte-macrophage colony stimulating factor (GM-CSF), IL-10, and transforming growth factor-beta (TGF-beta), and tumor cell expression of IL-10 and TGF-beta in situ in 49 primary colon carcinomas and 20 metastases using immunohistochemistry.RESULTS:
The percentage of primary colon carcinoma samples in which > 20% of TIL expressed each cytokine was as follows IL-4 47%; TNF-alpha 22%; TGF-beta 10%; IFN-gamma 6%; IL-22%; IL-10 0%; and GM-CSF 0%. Lymphocytes more commonly infiltrated colon carcinoma primaries than metastases, and TIL expression of IL-4 and TNF-alpha was more common in primary than metastastatic carcinomas. Expression of TNF-alpha by even a small proportion (> or = 3%) of the TIL in a colon carcinoma specimen was associated with better overall survival (P = 0.01) when compared with patients with little or no TIL TNF-alpha expression (5-year survival 82% vs. 47%). Expression of IL-4 by > or = 20% of colon carcinoma TIL was also associated with improved survival (P = 0.01; 5-year survival 87% vs. 50%). The expression of IL-10 or TGF-beta by colon carcinoma TIL or colon tumor cells themselves was not associated with impaired survival. Benign epithelial cells stained positively for IL-10 and TGF-beta more frequently than tumor cells (P < 0.001).CONCLUSIONS:
There are differences between the immune microenvironment of primary tumors and metastases. Although IL-10 is expressed by colon carcinoma cells and TIL, it is unlikely that it plays an important immunosuppressive role. TNF-alpha and IL-4 are commonly expressed by colon carcinoma TIL and both are associated with improved survival.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma
/
Cytokines
/
Lymphocytes, Tumor-Infiltrating
/
Interleukin-4
/
Tumor Necrosis Factor-alpha
/
Colonic Neoplasms
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cancer
Year:
1996
Document type:
Article
Affiliation country:
United States