Systematic analysis of the immunoregulation of murine neuroblastoma

Abstract

If immunoregulation of cancer is to be effective, the tumor must express immunogenicity and the host immune mechanism must be capable of responding to that stimulus. Though neuroblastoma (NB) might be such a tumor, a systematic assessment of this complex host-tumor interaction is lacking. We report such an analysis using the murine NB system. C1300-NB is highly antigenic, locally growing, and nonmetastasizing, while its clonal counterpart, TBJ-NB, is minimally antigenic and demonstrates not only aggressive local growth but systemic metastases as well. We analyzed A/J mouse antitumor naturally occurring killer lymphocyte (NK cells), cytotoxic lymphocyte (CTL cells), and suppressor lymphocyte (SC cells) function in response to these tumor lines. NK and CTL activity was measured in 40 mice after 3 weeks of growth of either C1300-NB or TBJ-NB using a cold target inhibition test to either the YAC-1 or P815 mastocytoma cell line, respectively. SC activity was analyzed in an additional 24 mice treated with an SC destroying 15 mg/kg of cyclophosphamide (CYA) three days after tumor inoculation. After 4 weeks of tumor growth spleens were harvested, cell-mediated cytotoxicity was measured by chromium 51 release assay and tumor cell lysis was expressed as lytic unit 30 (LU-30), an arbitrary definition of the number of lymphocytes needed to lyse 30% of target cells. By increasing the concentration of the NK-sensitive YAC-1 cold target, there was a 56.8% inhibition of lymphocytotoxicity to C1300-NB, contrasting with this was the lack of inhibition (17.8%) by the non-NK sensitive P815 cell line.(ABSTRACT TRUNCATED AT 250 WORDS)