Aston Wayne J, Hope Danika E, Cook Alistair M, Boon Louis, Dick Ian, Nowak Anna K, Lake Richard A, Lesterhuis W Joost
National Centre for Asbestos Related Diseases, The University of Western Australia, Nedlands, WA, Australia.
Medical School, The University of Western Australia, Nedlands, WA, Australia.
Oncoimmunology. 2019 Jul 13;8(11):e1641390. doi: 10.1080/2162402X.2019.1641390. eCollection 2019.
Dexamethasone is a synthetic glucocorticoid commonly used for the prevention and management of side effects in cancer patients undergoing chemotherapy. While it is effective as an anti-emetic and in preventing hypersensitivity reactions, dexamethasone depletes peripheral blood lymphocytes and impacts immune responses. The effect of dexamethasone on the number and quality of tumour-infiltrating leukocytes has not been reported. To address this, we calibrated the dose in two different strains of mice to achieve the same extent of peripheral blood lymphocyte depletion observed in patients with cancer. Doses that caused analogous depletion of T and B lymphocytes and NK cells from the peripheral blood, elicited no change in these populations within the tumour. The expression of immune checkpoint molecules PD-1, OX40, GITR and TIM3 on tumour-infiltrating lymphocytes was not altered. We found that dexamethasone had a small but significant deleterious impact on weakly efficacious chemoimmunotherapy but had no effect when the protocol was highly efficacious. Based on these results, we predict that dexamethasone will have a modest negative influence on the overall effectiveness of chemoimmunotherapy treatment.
地塞米松是一种合成糖皮质激素，常用于预防和处理接受化疗的癌症患者的副作用。虽然地塞米松作为一种止吐药以及预防过敏反应有效，但它会消耗外周血淋巴细胞并影响免疫反应。地塞米松对肿瘤浸润白细胞数量和质量的影响尚未见报道。为解决这一问题，我们在两种不同品系的小鼠中校准剂量，以达到在癌症患者中观察到的外周血淋巴细胞耗竭程度。导致外周血中T、B淋巴细胞和自然杀伤细胞类似耗竭的剂量，并未引起肿瘤内这些细胞群体的变化。肿瘤浸润淋巴细胞上免疫检查点分子PD-1、OX40、糖皮质激素诱导的肿瘤坏死因子受体（GITR）和T细胞免疫球蛋白黏蛋白分子3（TIM3）的表达未改变。我们发现地塞米松对疗效较弱的化学免疫疗法有微小但显著的有害影响，但当方案疗效高时则无影响。基于这些结果，我们预测地塞米松将对化学免疫疗法治疗的总体有效性产生适度的负面影响。
