The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients

Jiuxing Feng; Shujing Chen; Shuangqi Li; Baitong Wu; Jiacheng Lu; Li Tan; Jiamin Li; Yuanlin Song; Guoming Shi; Yujiang Geno Shi; Jinjun Jiang

doi:10.1016/j.tranon.2020.100865

The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients

Transl Oncol. 2020 Dec;13(12):100865. doi: 10.1016/j.tranon.2020.100865. Epub 2020 Sep 10.

Authors

Jiuxing Feng¹, Shujing Chen², Shuangqi Li¹, Baitong Wu³, Jiacheng Lu⁴, Li Tan¹, Jiamin Li², Yuanlin Song², Guoming Shi⁴, Yujiang Geno Shi⁵, Jinjun Jiang⁶

Affiliations

¹ Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
² Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ School of Medicine, Tongji University, Shanghai 200120, China.
⁴ Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁵ Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: Yujiang_shi@hms.harvard.edu.
⁶ Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: jiang.jinjun@zs-hospital.sh.cn.

Abstract

Monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small cell lung cancer (NSCLC). In this retrospective study, 27 advanced NSCLC patients were divided into partial response (PR), stable disease (SD), and progressive disease (PD) groups. The impact of anti-PD-1 therapy on circulating Tregs, G-MDSCs, and M-MDSCs was assessed by flow cytometer. Here, we found that anti-PD-1 treatment boosted circulating Tregs levels, which presented the most remarkable augment during the first two therapeutic cycles, in NSCLC patients. In contrast, anti-PD-1 therapy did not overall change G-MDSCs and M-MDSCs levels. However, the PR group had a higher baseline level of M-MDSCs, which exhibited a significant decrease after the first cycle of anti-PD-1 treatment. Besides, M-MDSCs levels in the PR group were maintained at a low level in the following therapeutic cycles. Consistently, Tregs levels robustly increased in the syngeneic tumor model after anti-mouse PD-1 Ab treatment. Accordingly, M-MDSCs neutralization by anti-mouse ly6c Ab enhanced the anti-tumor efficacy of anti-PD-1 therapy in mice. Finally, the decreased M-MDSCs levels were associated with the enhanced effector CD8⁺ T cells expansion in the PR group and mice. In conclusion, anti-PD-1 therapy upregulates Tregs levels in NSCLC patients, and the M-MDSC levels are associated with the anti-tumor efficacy of anti-PD-1 treatment. Neutralization of M-MDSCs may be a promising option to augment anti-PD-1 therapy efficacy in NSCLC.

Keywords: Anti-PD-1 therapy; Immunotherapy; M-MDSCs; NSCLC; Tregs.