Faculty Collaboration Database

Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes. Cancer Immunol Immunother 1996 May;42(4):237-45

Date

05/01/1996

Pubmed ID

8665571

Pubmed Central ID

PMC11037685

DOI

10.1007/s002620050276

Scopus ID

2-s2.0-0030001007 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

Author List

Arca MJ, Krauss JC, Strome SE, Cameron MJ, Chang AE

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Division
Cytokines
Female
Flow Cytometry
Immunotherapy, Adoptive
Lymph Nodes
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Phenotype
Transduction, Genetic
Vaccines