Power Robert, Lowery Maeve A, Reynolds John V, Dunne Margaret R
Department of Surgery, Trinity College Dublin, Dublin, Ireland.
Trinity St. James Cancer Institute, Trinity College Dublin, Dublin, Ireland.
Front Oncol. 2020 Jun 4;10:891. doi: 10.3389/fonc.2020.00891. eCollection 2020.
Immunotherapy has achieved long-term disease control in a proportion of cancer patients, but determinants of clinical benefit remain unclear. A greater understanding of antitumor immunity on an individual basis is needed to facilitate a precision oncology approach. A conceptual framework called the "cancer-immune set point" has been proposed to describe the equilibrium between factors that promote or suppress anticancer immunity and can serve as a basis to understand the variability in clinical response to immune checkpoint blockade. Oesophageal cancer has a high mutational burden, develops from pre-existing chronic inflammatory lesions and is therefore anticipated to be sensitive to immune checkpoint inhibition. However, both tumour- and patient-specific factors including the immune microenvironment, the microbiome, obesity, and host genetics contribute to an immune set point that confers a lower-than-expected response to checkpoint blockade. Immunotherapy is therefore currently confined to latter lines of treatment of advanced disease, with no reliable predictive biomarker of response. In this review, we examine oesophageal cancer in the context of the cancer-immune set point, discuss factors that contribute to response to immunotherapeutic intervention, and propose areas requiring further investigation to improve treatment response.
免疫疗法已在一定比例的癌症患者中实现了长期疾病控制，但临床获益的决定因素仍不清楚。需要在个体层面上更深入地了解抗肿瘤免疫，以推动精准肿瘤学方法的发展。一个名为“癌症免疫设定点”的概念框架已被提出，用于描述促进或抑制抗癌免疫的因素之间的平衡，并可作为理解免疫检查点阻断临床反应变异性的基础。食管癌具有高突变负荷，由先前存在的慢性炎症病变发展而来，因此预计对免疫检查点抑制敏感。然而，包括免疫微环境、微生物群、肥胖和宿主遗传学在内的肿瘤特异性和患者特异性因素都会导致免疫设定点，从而使对检查点阻断的反应低于预期。因此，免疫疗法目前仅限于晚期疾病的后线治疗，且没有可靠的反应预测生物标志物。在本综述中，我们在癌症免疫设定点的背景下研究食管癌，讨论影响免疫治疗干预反应的因素，并提出需要进一步研究以改善治疗反应的领域。
