Influence of primary tumor site on lymphocyte antitumor activity

Clinical Stage IV-S neuroblastoma involving a primary, the liver, bone marrow, and/or skin has a favorable prognosis despite a considerable tumor burden. In a pilot experiment utilizing mouse C 1300 neuroblastoma, we demonstrated that animals receiving tumor to IV-S sites had a prolonged survival. To analyze the role which liver modulation of tumor might play in an immunologically mediated host-antitumor response, we applied an in vitro lymphocyte blastogenesis assay. Host-tumor response as reflected by blastogenesis and as quantified by tritiated thymidine incorporation into DNA demonstrated that normal lymphocytes were stimulated to a greater degree by subcutaneous site tumor than by tumor from the liver (260.7 +/- 71.9 vs. -54.2 +/- 194.3 CPM, p less than 0.05). Sensitized lymphocytes harvested from liver tumor bearers demonstrated a greater response when admixed with subcutaneous tumor in vitro (771.9 +/- 300.4 vs. 45.9 +/- 277.5 CPM, p less than 0.05) and sensitized lymphocytes harvested from subcutaneous tumor bearing animals also demonstrated more in vitro blastogenesis to subcutaneous tumor (577.9 +/- 200.2 vs. 98.9 +/- 154.1 CPM, p less than 0.05). However, host lymphocytes were themselves comparably reactive whether they were harvested from liver tumor or subcutaneous tumor donors (771.9 +/- 300.4 vs. 577.9 +/- 200.2, p = NS). These data suggest that lymphocytes in contact with murine liver neuroblastoma respond less well than when in contact with subcutaneous site tumor, a form of afferent blockade which may account for the propensity of the liver to serve as a site for metastatic disease.