Fidler I J, Bucana C
Cancer Res. 1977 Nov;37(11):3945-56.
B16 melanoma variant lines, which resisted lysis by syngeneic lymphocytes, were selected in vitro by repeated exposure of the tumor cells to purified cytotoxic lymphocytes. The resistance of the tumor cells to lysis mediated by syngeneic lymphocytes was not accompanied by a loss or masking of major histocompatibility antigens. Neither the lymphocyte-susceptible B16 (F10) nor the lymphocyte-resistant B16 (F10Lr) cells grew in allogeneic recipients, and both were destroyed in vitro by allogeneic lymphocytes. The resistance to lysis by syngeneic lymphocytes was not accompanied by loss or masking of receptors for macrophage recognition and destruction. F10Lr cells did not protect F10 cells from lymphocyte-mediated lysis in cocultivation experiments. Immunization of syngeneic mice in vivo with B16-F10 cells successfully protected mice against challenge with B16-F10 cells. However, mice immunized with B16-F10Lr cells were not protected against challenge with B16-F10 cells. B16-F10Lr cells were not immunogenic when tested under this condition. Light, scanning, and transmission electron microscopic studies of tumor cell-lymphocyte interaction suggested that the resistance of B16-F10Lr cells to destruction by syngeneic lymphocytes in vitro was due to the masking or absence of tumor-specific antigen(s) present on the lymphocyte-susceptible F10 cells.
通过将肿瘤细胞反复暴露于纯化的细胞毒性淋巴细胞，在体外选择出对同基因淋巴细胞溶解具有抗性的B16黑色素瘤变异株系。肿瘤细胞对同基因淋巴细胞介导的溶解的抗性，并未伴随着主要组织相容性抗原的丧失或掩盖。淋巴细胞敏感的B16（F10）细胞和淋巴细胞抗性的B16（F10Lr）细胞在异基因受体中均不生长，并且在体外均被异基因淋巴细胞破坏。对同基因淋巴细胞溶解的抗性，并未伴随着巨噬细胞识别和破坏受体的丧失或掩盖。在共培养实验中，F10Lr细胞不能保护F10细胞免受淋巴细胞介导的溶解。用B16-F10细胞对同基因小鼠进行体内免疫，成功地保护小鼠免受B16-F10细胞的攻击。然而，用B16-F10Lr细胞免疫的小鼠不能免受B16-F10细胞的攻击。在此条件下测试时，B16-F10Lr细胞没有免疫原性。对肿瘤细胞-淋巴细胞相互作用的光镜、扫描电镜和透射电镜研究表明，B16-F10Lr细胞在体外对同基因淋巴细胞破坏的抗性，是由于淋巴细胞敏感的F10细胞上存在的肿瘤特异性抗原被掩盖或缺失。
