A costimulatory signal through B7 to its counter-receptor CD28 on T cells enhances T cell activation. We have generated recombinant retroviruses containing cDNA for murine B7 and transduced a panel of murine tumor lines with varying immunogenicity to study the effect of B7 costimulation on antitumor immunity. In contrast to the progressive outgrowth of all wild-type (B7-) tumors in unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4, mastocytoma P815, and melanoma E6B2, regressed completely when transduced with the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102, and Ag104, and melanoma B16, remained tumorigenic after transduction of the B7 gene. Immunization with B7-transduced immunogenic tumors enhanced protective immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the respective wild-type tumors as compared to immunization with nontransduced or mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4 cells augmented the specificity of tumor-reactive CTL in long-term cultures. Treatment by injection of B7-transduced tumor cells cured 60% of mice with established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic tumors transduced with B7 did not provide protective immunity and did not increase specific CTL activity. Our results show that tumor immunogenicity is critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.
Article|
February 01 1994
Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.
L Chen,
L Chen
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
P McGowan,
P McGowan
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
S Ashe,
S Ashe
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
J Johnston,
J Johnston
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
Y Li,
Y Li
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
I Hellström,
I Hellström
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
K E Hellström
K E Hellström
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Search for other works by this author on:
L Chen
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
P McGowan
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
S Ashe
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
J Johnston
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Y Li
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
I Hellström
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
K E Hellström
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (2): 523–532.
Citation
L Chen, P McGowan, S Ashe, J Johnston, Y Li, I Hellström, K E Hellström; Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.. J Exp Med 1 February 1994; 179 (2): 523–532. doi: https://doi.org/10.1084/jem.179.2.523
Download citation file: