Palucka A Karolina, Coussens Lisa M
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA; Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Department of Cell, Developmental & Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code L215, Room 5508, Richard Jones Hall, Portland, OR 97239-3098, USA.
Cell. 2016 Mar 10;164(6):1233-1247. doi: 10.1016/j.cell.2016.01.049.
Cancer heterogeneity, a hallmark enabling clonal survival and therapy resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T-cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that, if better harnessed, could significantly enhance the efficacy of cytotoxic therapy and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled. These include developing strategies for neutralizing tumor-promoting inflammation, broadening T-cell repertoires (via vaccination), and elucidating the mechanisms by which immune cells organize tumor microenvironments to regulate T-cell activity. Such efforts will pave the way for identifying new targets for combination therapies that overcome resistance to current treatments and promote long-term cancer control.
癌症异质性是克隆存活和治疗抗性的一个标志，它由活跃的免疫反应塑造而成。抗原特异性T细胞能够控制癌症，过继性T细胞转移和检查点阻断等免疫疗法在临床上已证实了这一点。因此，宿主免疫系统是一个强大的工具，如果能更好地加以利用，就能显著提高细胞毒性疗法的疗效，并改善癌症患者的治疗结果。然而，要实现这一愿景，必须攻克多个研究前沿领域。这些领域包括制定中和促肿瘤炎症的策略、拓宽T细胞库（通过疫苗接种），以及阐明免疫细胞组织肿瘤微环境以调节T细胞活性的机制。这些努力将为确定联合疗法的新靶点铺平道路，这些联合疗法能够克服对现有治疗的抗性，并促进对癌症的长期控制。
