PT  - JOURNAL ARTICLE
AU  - Felsher, Dean W.
AU  - Rhim, Sung-Hee
AU  - Braun, Jonathan
TI  - A Murine Model for B-Cell Lymphomagenesis in Immunocompromised Hosts: Natural Killer Cells Are an Important Component of Host Resistance to Premalignant B-Cell Lines
DP  - 1990 Nov 01
TA  - Cancer Research
PG  - 7050--7056
VI  - 50
IP  - 21
4099  - http://cancerres.aacrjournals.org/content/50/21/7050.short
4100  - http://cancerres.aacrjournals.org/content/50/21/7050.full
SO  - Cancer Res1990 Nov 01; 50
AB  - The accompanying paper (D. W. Felsher et al., Cancer Res., 50: 7042–7049, 1990) describes a new panel of cloned murine B-cell lines with a premalignant phenotype and in vivo-derived malignant variants. This paper assesses the contribution of immune mediated antitumor mechanisms which might account for host resistance to the tumorigenicity of these cell lines. Conventional T-cell-dependent responses did not appear to be critical to host resistance. In vivo elimination of T-helper cells with anti-L3T4 monoclonal antibody did not reduce host resistance to the tumorigenicity of these cell lines, nor did these cell lines elicit cytotoxic T-cell activity. However, a strong correlation was found between tumorigenicity and host natural killer (NK) activity. In vitro studies demonstrated that the cell lines were as NK sensitive as the prototypical NK target, YAC-1, whereas the malignant variants fully tumorigenic in normal hosts were >20-fold less NK sensitive than were the parent cell lines. In vivo depletion of NK cells with anti-asialo-GM1 in BALB/c strongly diminished host resistance to cell line tumorigenicity, whereas polydeoxyinosinic-deoxycytidilic acid induction of NK cells enhanced host resistance. These findings indicate that NK function is a critical component to host resistance in this system and suggest that endogenous cellular mechanisms which overcome NK sensitivity could be a target for secondary transforming events in B-cell lymphomagenesis. They also raise the unexpected possibility that a non-antigen-dependent (versus immune cytotoxic T-lymphocytes) effector mechanism may be the key deficit promoting B-cell neoplasia in the setting of immunocompromised states. ©1990 American Association for Cancer Research.