Calhoun R F, Naziruddin B, Enriquez-Rincon F, Duffy B F, Ritter J M, Sundaresan S, Patterson G A, Cooper J D, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Surgery. 2000 Jul;128(1):76-85. doi: 10.1067/msy.2000.106639.
Cancer-associated, major histocompatibility complex (MHC)-restricted peptide antigens have been elucidated in human melanomas and ovarian, breast, and renal carcinomas; but relatively little is known about lung cancer antigens.
To work toward delineation of lung cancer-associated antigens, we developed tumor infiltrating lymphocytes (TILs), peripheral blood mononuclear cell-derived cytolytic T cell lines (CTL), autologous lung cancer cell lines, and normal lung cell lines from 17 patients undergoing lung cancer resections. The TILs and CTL lines were subsequently evaluated for markers of activation and specific lysis of autologous or allogeneic lung cancer cell lines or both.
Freshly isolated TILs contained a more activated T cell population compared with the patients' peripheral blood T cells as evidenced by an increased expression of HLA-DR, CD25, and CD45RO. TILs isolated from 15 patients lysed allogeneic lung cancer lines. TILs lysed autologous lung cancer but not autologous normal lung or Epstein-Barr virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity. A CTL line (RHPBL57.1) was generated from peripheral blood mononuclear cells of an HLA-A24(+) patient by stimulation against an established HLA-A24(+) allogeneic lung cancer cell line. RHPBL57.1 lysed the lung cancer cell line in an HLA-A24-restricted manner. Moreover, RHPBL57.1 specifically lysed autologous B-LCL pulsed with peptides, eluted from MHC class I and isolated from the HLA-A24(+) lung cancer cell line.
TILs isolated from patients with lung cancer are predominantly an activated population of T cells with evidence of tumor and MHC class I-restricted lysis. Furthermore, we provide evidence for a lung cancer-associated, MHC class I-bound peptide antigen(s) that reconstitutes the epitope recognized by a lung cancer specific CD8(+) T cell line derived from a patient with lung cancer.
在人类黑色素瘤、卵巢癌、乳腺癌和肾癌中已阐明了与癌症相关的、主要组织相容性复合体（MHC）限制性肽抗原；但对肺癌抗原的了解相对较少。
为了致力于肺癌相关抗原的鉴定，我们从17例接受肺癌切除术的患者中培养了肿瘤浸润淋巴细胞（TIL）、外周血单个核细胞来源的细胞毒性T细胞系（CTL）、自体肺癌细胞系和正常肺细胞系。随后对TIL和CTL系进行活化标志物评估以及对自体或同种异体肺癌细胞系或两者的特异性杀伤评估。
与患者外周血T细胞相比，新鲜分离的TIL含有更多活化的T细胞群体，HLA-DR、CD25和CD45RO表达增加证明了这一点。从15例患者中分离的TIL裂解了同种异体肺癌细胞系。在8例测试病例中的4例中，TIL裂解了自体肺癌细胞，但未裂解自体正常肺细胞或爱泼斯坦-巴尔病毒转化的B细胞系（B-LCL），提示肿瘤特异性。通过用已建立的HLA-A24(+)同种异体肺癌细胞系刺激，从一名HLA-A24(+)患者的外周血单个核细胞中产生了一个CTL系（RHPBL57.1）。RHPBL57.1以HLA-A24限制性方式裂解肺癌细胞系。此外，RHPBL57.1特异性裂解了用从HLA-A24(+)肺癌细胞系的MHC I类洗脱并分离的肽脉冲处理的自体B-LCL。
从肺癌患者中分离的TIL主要是活化的T细胞群体，有肿瘤和MHC I类限制性杀伤的证据。此外，我们提供了一种与肺癌相关的、MHC I类结合肽抗原的证据，该抗原重构了来自肺癌患者的肺癌特异性CD8(+) T细胞系识别的表位。
