Waller Edmund K
Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory University, 1365-C Clifton Road NE, Atlanta, Georgia 30322, USA.
Oncologist. 2007;12 Suppl 2:22-6. doi: 10.1634/theoncologist.12-S2-22.
GM-CSF stimulates the differentiation of hematopoietic progenitors to monocytes and neutrophils, and reduces the risk for febrile neutropenia in cancer patients. GM-CSF also has been shown to induce the differentiation of myeloid dendritic cells (DCs) that promote the development of T-helper type 1 (cellular) immune responses in cognate T cells. This review summarizes some of the immunological effects of GM-CSF relevant to antitumor immunity in cancer patients. GM-CSF has been used to augment the activity of rituximab in patients with follicular lymphoma and to induce autologous antitumor immunity in patients with hormone-refractory prostate cancer. GM-CSF causes upregulation of costimulatory molecule expression on leukemia blasts in vitro, enhancing their ability to present antigen to allogeneic T cells, and, in combination with interferon-alpha, can induce antitumor immune responses in patients whose acute leukemia has relapsed following allogeneic hematopoietic progenitor cell transplant. Tumor cells engineered to secrete GM-CSF are particularly effective as antitumor vaccines, and the addition of GM-CSF to standard vaccines may increase their effectiveness by recruiting DCs to the site of vaccination. However, a significant limitation in the use of GM-CSF as an immunostimulatory agent is that objective antitumor responses are infrequent, and are often not durable. Effective and durable antitumor immunity will likely require novel methods to eliminate counterregulatory immune responses that limit activation and expansion of cytotoxic T cells with antitumor activity.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）可刺激造血祖细胞分化为单核细胞和中性粒细胞，并降低癌症患者发热性中性粒细胞减少的风险。GM-CSF还被证明可诱导髓样树突状细胞（DCs）分化，从而促进同源T细胞中辅助性T细胞1型（细胞性）免疫反应的发展。本综述总结了GM-CSF与癌症患者抗肿瘤免疫相关的一些免疫效应。GM-CSF已被用于增强滤泡性淋巴瘤患者中利妥昔单抗的活性，并在激素难治性前列腺癌患者中诱导自体抗肿瘤免疫。GM-CSF可导致白血病原始细胞在体外共刺激分子表达上调，增强其向同种异体T细胞呈递抗原的能力，并且与α干扰素联合使用，可在异基因造血祖细胞移植后急性白血病复发的患者中诱导抗肿瘤免疫反应。经基因工程改造分泌GM-CSF的肿瘤细胞作为抗肿瘤疫苗特别有效，并且在标准疫苗中添加GM-CSF可能通过将DCs募集到接种部位来提高其有效性。然而，将GM-CSF用作免疫刺激剂的一个重大限制是客观的抗肿瘤反应很少见，而且往往不持久。有效且持久的抗肿瘤免疫可能需要新的方法来消除限制具有抗肿瘤活性的细胞毒性T细胞激活和扩增的反调节免疫反应。
