Apiranthitou-Drogari M, Paganin C, Bernasconi S, Losa G, Maneo A, Colombo N, Mantovani A, Allavena P
Laboratory of Immunology, Mario Negri Institute, Milano, Italy.
Cancer Immunol Immunother. 1992;35(4):289-95. doi: 10.1007/BF01789337.
Lymphocytes infiltrating human ovarian carcinoma obtained directly from the tumour mass (tumour-infiltrating lymphocytes, TIL) or from the carcinomatous ascites (tumour-associated lymphocytes, TAL) were expanded in vitro in long-term cultures with interleukin-2 and tested for their specific cytolytic activity. Killing of the autologous tumour was detected only in a proportion of the patients, less frequently in TIL compared to TAL. In fact two out of ten TIL and four out of nine TAL cultures tested showed significant levels of lysis against the autologous tumour. This cytotoxic activity was not restricted to the autologous tumour, as other tumour cell lines, including non-ovarian ones, were lysed as well. The cultures that were not cytotoxic against the autologous tumour were in most cases able to lyse other tumour cell lines of ovarian or other histology. Cloning of TIL from one patient was performed: of 22 clones tested, 4 displayed higher cytotoxicity against the autologous tumour compared to the uncloned population and 3 out of these 4 did not kill an irrelevant carcinoma cell line. In order to stimulate the expansion of putative specific effectors we performed mixed lymphocyte/tumour cultures (MLTC) with autologous or allogeneic tumour cells. No stimulation of cytotoxicity against the autologous tumour was detected after MLTC in nine different TAL populations, using autologous or allogeneic tumours as stimulators. On the contrary, peripheral blood lymphocytes from two patients after MLTC with the autologous tumour showed increased killing of the autologous and decreased killing of an allogeneic target. In conclusion TIL and TAL from ovarian carcinoma expanded in vitro with interleukin-2 usually have non-MHC-restricted cytotoxicity and variable degrees of reactivity against the autologous tumour. A preferential killing for the autologous tumour was not observed even after MLTC. These results do not exclude the existence of tumour-specific cytotoxic T lymphocytes in ovarian carcinoma; nevertheless they suggest that putative specific effectors have very low frequency and that culture techniques for expanding their growth more selectively are still to be optimized.
直接从肿瘤块获取的浸润人卵巢癌的淋巴细胞（肿瘤浸润淋巴细胞，TIL）或从癌性腹水中获取的淋巴细胞（肿瘤相关淋巴细胞，TAL），在白细胞介素-2的长期培养下于体外扩增，并检测其特异性细胞溶解活性。仅在部分患者中检测到对自体肿瘤的杀伤作用，与TAL相比，TIL中这种情况较少见。实际上，在检测的10个TIL培养物中有2个以及9个TAL培养物中有4个显示出对自体肿瘤的显著裂解水平。这种细胞毒性活性并不局限于自体肿瘤，其他肿瘤细胞系，包括非卵巢来源的，也会被裂解。在大多数情况下，对自体肿瘤无细胞毒性的培养物能够裂解卵巢或其他组织学类型的其他肿瘤细胞系。对一名患者的TIL进行了克隆：在检测的22个克隆中，4个对自体肿瘤显示出比未克隆群体更高的细胞毒性，并且这4个中的3个不会杀伤无关的癌细胞系。为了刺激假定的特异性效应细胞的扩增，我们用自体或同种异体肿瘤细胞进行了混合淋巴细胞/肿瘤培养（MLTC）。在9个不同的TAL群体中，使用自体或同种异体肿瘤作为刺激物进行MLTC后，未检测到对自体肿瘤细胞毒性的刺激作用。相反，两名患者的外周血淋巴细胞在与自体肿瘤进行MLTC后，对自体肿瘤的杀伤作用增强，而对同种异体靶标的杀伤作用减弱。总之，用白细胞介素-2在体外扩增的卵巢癌TIL和TAL通常具有非主要组织相容性复合体（MHC）限制的细胞毒性以及对自体肿瘤的不同程度反应性。即使在MLTC后，也未观察到对自体肿瘤的优先杀伤作用。这些结果不排除卵巢癌中存在肿瘤特异性细胞毒性T淋巴细胞；然而，它们表明假定的特异性效应细胞频率非常低，并且用于更选择性地扩大其生长的培养技术仍有待优化。
