Marsili M A, Walker M C, Phillips-Quagliata J M
Cancer Res. 1986 Jan;46(1):190-7.
BALB/cJ X C57BL/10Sn F1 (hereafter called B10F1) hybrids resist challenge with the BALB/c plasmacytoma, MPC-11, by a radiation-sensitive, silica-insensitive mechanism, whereas BALB/cJ X BALB.B F1 (hereafter called BALB.BF1) hybrids are as susceptible to MPC-11 as are homozygous BALB/c mice themselves. To investigate the mechanism of resistance, we have compared anti-MPC-11 immune responses by these F1 hybrids both before and at various times after tumor challenge. Resistance is not determined by natural killer cell reactivity inasmuch as neither hybrid harbors splenic natural killer cells with lytic activity directed against MPC-11. Nor is it determined by antibody-dependent cell-mediated cytotoxicity since neither hybrid produces an appropriate anti-MPC-11 antibody. Spleen cells and lymph node cells from both hybrids are capable of generating high levels of anti-MPC-11 cytotoxic T-lymphocyte activity in both primary and secondary mixed-lymphocyte tumor cell cultures. Such cytotoxic T-lymphocytes protect susceptible hybrids from tumor growth in Winn assays. The susceptible but not the resistant hybrids lose the ability to generate high levels of cytotoxic T-lymphocytes activity in spleen mixed lymphocyte tumor cell cultures by 28 days, and in lymph node mixed-lymphocyte tumor cell cultures by 14 days postchallenge. The reduction in spleen cell reactivity is due to suppression mainly by adherent cells and can be abrogated by pretreatment of the susceptible hybrids with a low dose of Cytoxan 2 days before challenge. This pretreatment does not, however, protect the mice. They develop tumor at the same rate and die at the same time as do controls. Both the late appearance of suppression and the lack of effect on survival of its ablation suggest it to be a concomitant of tumor growth rather than its cause. Resistance to tumor growth in this model system may reflect an enhanced ability of the resistant hybrid to deliver effector cells to the site of tumor implantation.
BALB/cJ×C57BL/10Sn F1（以下简称B10F1）杂交小鼠通过一种对辐射敏感、对二氧化硅不敏感的机制抵抗BALB/c浆细胞瘤MPC-11的攻击，而BALB/cJ×BALB.B F1（以下简称BALB.BF1）杂交小鼠对MPC-11的易感性与纯合BALB/c小鼠本身相同。为了研究抵抗机制，我们比较了这些F1杂交小鼠在肿瘤攻击前及攻击后不同时间的抗MPC-11免疫反应。抵抗不是由自然杀伤细胞反应性决定的，因为两种杂交小鼠的脾脏中都没有对MPC-11具有裂解活性的自然杀伤细胞。它也不是由抗体依赖性细胞介导的细胞毒性决定的，因为两种杂交小鼠都不产生合适的抗MPC-11抗体。两种杂交小鼠的脾细胞和淋巴结细胞在原发性和继发性混合淋巴细胞肿瘤细胞培养中都能够产生高水平的抗MPC-11细胞毒性T淋巴细胞活性。这种细胞毒性T淋巴细胞在Winn试验中可保护易感杂交小鼠免受肿瘤生长。易感但非抗性杂交小鼠在攻击后28天内在脾混合淋巴细胞肿瘤细胞培养中以及在攻击后14天内在淋巴结混合淋巴细胞肿瘤细胞培养中失去产生高水平细胞毒性T淋巴细胞活性的能力。脾细胞反应性的降低主要是由于贴壁细胞的抑制作用，并且可以通过在攻击前2天用低剂量的环磷酰胺预处理易感杂交小鼠来消除这种抑制作用。然而，这种预处理并不能保护小鼠。它们的肿瘤生长速度和死亡时间与对照组相同。抑制作用的延迟出现及其消除对生存无影响这两点都表明它是肿瘤生长的伴随现象而非原因。在这个模型系统中对肿瘤生长的抗性可能反映了抗性杂交小鼠将效应细胞输送到肿瘤植入部位的能力增强。
