An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis.
OBJECTIVE
Immunotherapy using interleukin 2 has had disappointing results in the treatment of colon cancer. Overcoming escape mechanisms, such as lack of antigen presentation and absence of accessory adhesion molecules on cancer cells, may increase its efficiency. We tried to do so by modifying the phenotype of the weakly immunogenic rat colon cancer PROb cells with sodium butyrate.


METHODS
After in vitro treatment with butyrate, PROb cells were tested for lymphokine-activated killer cell sensitivity and, using cytofluorometry, expression of adhesion molecules. We then treated established PROb peritoneal carcinomatoses with intraperitoneal injections of interleukin 2 and butyrate. Tumors were studied histologically and immunohistochemically. We tested the specificity of the immune protection by subsequent subcutaneous challenges with either PROb or glioma cells and by Winn's assay.


RESULTS
Butyrate increased lymphokine-activated killer cell sensitivity and expression of major histocompatibility complex class I and intercellular adhesion molecule 1 in vitro. Interleukin 2/butyrate combination resulted in cases of complete cure of carcinomatosis with specific protection against PROb cells. We noticed a complex stroma reaction with numerous functional antigen presenting cells close to PROb cells.


CONCLUSIONS
The complete regression of tumor masses may be attributed, at least in part, to a butyrate-induced increase in immunogenicity of the cancer cells. This new combined immunotherapy may be of interest in the treatment of colon cancer.
INSERM Contrat Jeune Formation 90-11, Institute of Biology, University of Medicine, Nantes, France.
P
P
Perrin
E
E
Cassagnau
C
C
Burg
Y
Y
Patry
F
F
Vavasseur
J
J
Harb
J
J
Le Pendu
J Y
JY
Douillard
J P
JP
Galmiche
F
F
Bornet
D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002087:Butyrates / Q000627:therapeutic use*; D020148:Butyric Acid; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000276:immunology
D002087:Butyrates; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D020148:Butyric Acid; D018799:Intercellular Adhesion Molecule-1