Peoples G E, Schoof D D, Andrews J V, Goedegebuure P S, Eberlein T J
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115.
Surgery. 1993 Aug;114(2):227-34.
The existence of a tumor-specific T-cell immune response to human malignant melanoma has been well documented. In contrast, the existence of tumor-specific cytotoxic T lymphocyte to ovarian cancer remains controversial despite the abundant lymphocytic infiltrates in the malignant ascites and solid tumor of these patients.
Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumors were isolated from six untreated patients with ovarian cancer. TAL and TIL were grown with initial anti-cluster of differentiation of T cells (CD3), low-dose interleukin-2, and tumor stimulation. T-cell lines were analyzed in functional studies.
At 5 weeks, TAL and TIL from five of six patients were > 50% CD8+, and one of six was > 70% CD4+. In all five pairs of CD8 positive cultures, both TAL and TIL exhibited high levels of tumor-specific cytotoxicity for ascite and solid tumor, respectively. T-cell recognition of tumor was mediated through the T-cell receptor-CD3 complex and was human leukocyte antigen class I restricted. TAL and TIL lysed autologous ascitic tumor equally well; however, TAL-mediated tumoricidal activity against autologous solid tumor was consistently and significantly poorer than TIL-mediated killing.
Tumor-specific cytotoxic T lymphocytes can be expanded from both TAL and TIL. However, TAL do not kill solid tumor as efficiently as TIL. This suggests the requirement of TIL, or a combination of TIL and TAL, for effective immunotherapy.
针对人类恶性黑色素瘤的肿瘤特异性T细胞免疫反应的存在已有充分记录。相比之下，尽管这些患者的恶性腹水中有大量淋巴细胞浸润，实体瘤中也有淋巴细胞浸润，但针对卵巢癌的肿瘤特异性细胞毒性T淋巴细胞的存在仍存在争议。
从6例未经治疗的卵巢癌患者中分离出恶性腹水中的肿瘤相关淋巴细胞（TAL）和实体瘤中的肿瘤浸润淋巴细胞（TIL）。TAL和TIL在初始抗T细胞分化簇（CD3）、低剂量白细胞介素-2和肿瘤刺激下培养。对T细胞系进行功能研究分析。
5周时，6例患者中有5例的TAL和TIL中CD8+细胞>50%，6例中有1例CD4+细胞>70%。在所有5对CD8阳性培养物中，TAL和TIL分别对腹水和实体瘤表现出高水平的肿瘤特异性细胞毒性。T细胞对肿瘤的识别通过T细胞受体-CD3复合物介导，且受人类白细胞抗原I类限制。TAL和TIL对自体腹水肿瘤的杀伤效果相同；然而，TAL介导的对自体实体瘤的杀瘤活性始终明显低于TIL介导的杀伤。
肿瘤特异性细胞毒性T淋巴细胞可从TAL和TIL中扩增。然而，TAL对实体瘤的杀伤效率不如TIL。这表明有效的免疫治疗需要TIL，或TIL与TAL的联合使用。
