Litzinger Mary T, Foon Kenneth A, Sabzevari Helen, Tsang Kwong-Yok, Schlom Jeffrey, Palena Claudia
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancer Immunol Immunother. 2009 Jun;58(6):955-65. doi: 10.1007/s00262-008-0611-5. Epub 2008 Nov 14.
In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T cells exhibit dysfunction. We previously demonstrated that infection of CLL cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) increased expression of these costimulatory molecules on the surface of CLL cells and thus augmented their antigen-presenting capability. Here, we evaluate the effect of MVA-TRICOM-modified CLL cells on T cells. Following incubation with irradiated MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4(+) and CD8(+) T cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show that this increase was the result of physical acquisition from the antigen-presenting cells (APCs), and that purified T cells that acquired costimulatory molecules from MVA-TRICOM-modified CLL cells were able to stimulate the proliferation of untreated T cells. These results demonstrate for the first time that T cells from CLL patients can acquire multiple costimulatory molecules from autologous CLL cells and can then act as APCs themselves. Given the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting function of CLL cells and T cells simultaneously could be a distinct advantage in the effort to elicit antitumor immune responses.
在慢性淋巴细胞白血病（CLL）中，恶性B细胞和非恶性T细胞均表现出功能障碍。我们之前证明，用表达共刺激分子B7-1、细胞间黏附分子-1（ICAM-1）和淋巴细胞功能相关抗原-3（LFA-3）（命名为TRICOM）的改良安卡拉痘苗病毒（MVA）感染CLL细胞，可增加这些共刺激分子在CLL细胞表面的表达，从而增强其抗原呈递能力。在此，我们评估MVA-TRICOM修饰的CLL细胞对T细胞的影响。用经辐照的MVA-TRICOM修饰的CLL细胞孵育后，同种异体和自体CD4(+)和CD8(+) T细胞表达的B7-1、ICAM-1和LFA-3水平显著更高。我们发现这种增加是从抗原呈递细胞（APC）物理获取的结果，并且从MVA-TRICOM修饰的CLL细胞获取共刺激分子的纯化T细胞能够刺激未处理T细胞的增殖。这些结果首次证明，CLL患者的T细胞可以从自体CLL细胞获取多种共刺激分子，然后自身可充当APC。鉴于CLL的免疫缺陷特征，在引发抗肿瘤免疫反应的努力中，同时增强CLL细胞和T细胞的抗原呈递功能可能具有明显优势。
