Zumwalt Timothy J, Goel Ajay
Center for Gastrointestinal Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
Curr Colorectal Cancer Rep. 2015 Jun 1;11(3):125-140. doi: 10.1007/s11888-015-0269-2. Epub 2015 Jun 29.
Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although, many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized antitumor immune cells against malignancies, nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy - of which benefit less than 10% of those receiving therapy. After decades of progress, however, new insights into the mechanisms of immunosuppression, tolerance, and mutation profiling established novel therapies that circumvent these immunological barriers. This review underlines the most exciting methods to date that manipulate immune cells to curb mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint inhibitor antibodies - of which hint at effective and enduring protection against disease progression and undetected micrometastases.
复发性或转移性结直肠癌(mCRC)患者的长期生存率极低,而化疗干预和放射治疗等传统治疗方法对延长寿命的作用甚微。尽管最近证实,许多涉及免疫监视和免疫抑制的因素对患者的预后和护理至关重要,但旨在对抗无法切除的mCRC的多种实验性免疫疗法,在少数情况下,成功地动员了抗肿瘤免疫细胞对抗恶性肿瘤,也没有最终或持续地通过免疫疗法给予保护、完全缓解和/或疾病稳定——受益的患者不到接受治疗者的10%。然而,经过数十年的进展,对免疫抑制、耐受和突变谱机制的新见解确立了规避这些免疫障碍的新疗法。本综述强调了迄今为止最令人兴奋的操纵免疫细胞以抑制mCRC的方法,包括过继性细胞疗法、树突状细胞疫苗和检查点抑制剂抗体——这些方法有望有效且持久地预防疾病进展和未检测到的微转移。