Presence of an eosinophilic infiltrate in cervical squamous carcinoma results from a type 2 immune response.
OBJECTIVE
The presence of an eosinophilic infiltrate in patients with cervical squamous carcinoma has been shown to correlate with a worse overall survival, suggesting a less effective immune response in these cases. Since type 2 cytokines such as IL-4 and IL-5 are known to attract eosinophilic granulocytes, an immunohistochemical study was performed to gain further insight as to whether a type 1 or type 2 immune response is involved in eliciting an eosinophilic infiltrate.


METHODS
Frozen tissue sections of 9 normal cervical tissues, 23 premalignant cervical lesions, and 23 cervical squamous carcinomas were stained by immunohistochemistry with monoclonal antibodies directed against IFN-gamma and IL-4 as representatives of a type 1 or a type 2 response, respectively.


RESULTS
Normal tissues and premalignant lesions of the cervix did not contain eosinophilic granulocytes and showed very few IL-4- and IFN-gamma-positive cells. In cervical carcinoma the presence of IL-4 on tumor infiltrating cells correlated with the presence of eosinophilic granulocytes in the tumor (P value <0.01) and stroma (P value <0.05). IFN-gamma-positive cells did not show any such correlation. In addition, colocalization was observed of CD3- and IL-4-positive T lymphocytes indicating that IL-4 production is mediated by T lymphocytes.


CONCLUSIONS
The relative increase of IL-4-positive cells in the presence of an eosinophilic infiltrate might thus reflect an imbalance between a type 1 and type 2 response, in favor of the latter. Since a type 1 response stimulates an adequate cellular response which is negatively regulated by type 2 cytokines, these findings might explain the worse clinical outcome seen in cervical cancer patients with an eosinophilic tumor infiltrate. These results may have implications when developing immunotherapeutical strategies for cervical cancer.
Department of Gynecology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
W J
WJ
van Driel
P
P
Kievit-Tyson
L C
LC
van den Broek
A H
AH
Zwinderman
B J
BJ
Trimbos
G J
GJ
Fleuren
D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000276:immunology / Q000473:pathology
D015847:Interleukin-4; D007371:Interferon-gamma