Leong S P, Zhou Y M, Granberry M E, Wang T F, Grogan T M, Spier C, White R, Mehta A, Lin A Y
Department of Surgery, University of Arizona, Tucson 85724, USA.
Cancer Immunol Immunother. 1995 Jun;40(6):397-409. doi: 10.1007/BF01525391.
Metastatic or tumor-draining lymph nodes from six of nine melanoma patients undergoing lymph node dissection for metastatic melanoma generated cytotoxic T cells against autologous melanoma when these lymph node cells were treated by in vitro sensitization and recombinant interleukin-2 (IL-2). During the initial lymphocyte culture (2-6 weeks), cross-reactivity with autologous tumor cells, K562 and Daudi cells was usually noted. Cold-target inhibition assay with K562 and Daudi showed K562/Daudi-associated antigens on melanoma cells. During the later phase of lymphocyte culture with repeated in vitro sensitization (over 6-10 weeks), cytotoxicity was noted against autologous and allogeneic melanoma cells but not against K562. Daudi cells or autologous fibroblasts. Repeated in vitro sensitization resulted in the selection of specific cytotoxic lymphocytes against melanoma. Cold-target inhibition assay with autologous and allogeneic melanoma cells revealed shared and individual antigens. Using blocking monoclonal antibodies, MHC-restricted killing was noted in the autologous system. Further, both the autologous and allogeneic systems could be mediated through adhesion molecules such as ICAM-1 and LFA-3 on melanoma cells and LFA-1 on T cells. This study suggests that a constellation of cytotoxic effector cells and melanoma-associated antigens may be pivotal in tumor killing. Thus, future adoptive immunotherapy should modulate and enhance this complex interaction.
9名因转移性黑色素瘤接受淋巴结清扫术的黑色素瘤患者中，有6名患者的转移性或肿瘤引流淋巴结在经体外致敏和重组白细胞介素-2（IL-2）处理后，产生了针对自体黑色素瘤的细胞毒性T细胞。在初始淋巴细胞培养（2 - 6周）期间，通常会观察到与自体肿瘤细胞、K562和Daudi细胞的交叉反应性。用K562和Daudi进行的冷靶抑制试验显示黑色素瘤细胞上存在K562/Daudi相关抗原。在淋巴细胞培养后期，经反复体外致敏（超过6 - 10周），观察到对自体和同种异体黑色素瘤细胞具有细胞毒性，但对K562、Daudi细胞或自体成纤维细胞无细胞毒性。反复体外致敏导致选择出针对黑色素瘤的特异性细胞毒性淋巴细胞。用自体和同种异体黑色素瘤细胞进行的冷靶抑制试验揭示了共同抗原和个体抗原。使用阻断性单克隆抗体，在自体系统中观察到了MHC限制的杀伤作用。此外，自体和同种异体系统均可通过黑色素瘤细胞上的ICAM-1和LFA-3以及T细胞上的LFA-1等黏附分子介导。这项研究表明，一群细胞毒性效应细胞和黑色素瘤相关抗原可能在肿瘤杀伤中起关键作用。因此，未来的过继性免疫疗法应调节和增强这种复杂的相互作用。
