The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients
| Autor: | Baitong Wu, Jiuxing Feng, Jiamin Li, Guo-Ming Shi, Yujiang Geno Shi, Jia-Cheng Lu, Li Tan, Shuangqi Li, Shujing Chen, Yuanlin Song, Jinjun Jiang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Anti-PD-1 therapy Tregs NSCLC lcsh:RC254-282 Neutralization law.invention 03 medical and health sciences 0302 clinical medicine Stable Disease Immunity law medicine Original Research business.industry Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Myeloid-derived Suppressor Cell Cancer research Suppressor M-MDSCs business CD8 Progressive disease |
| Zdroj: | Translational Oncology Translational Oncology, Vol 13, Iss 12, Pp 100865-(2020) |
| ISSN: | 1936-5233 |
| DOI: | 10.1016/j.tranon.2020.100865 |
| Popis: | 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. Highlights • Anti-PD-1 therapy upregulates Tregs levels in NSCLC patients and mouse model. • M-MDSCs exhibit a significant decrease in the PR group after anti-PD-1 therapy. • M-MDSCs neutralization augments anti-PD-1 efficacy in mouse model. • The increased effector CD8+ T cells are associated with the better anti-PD-1 efficacy in the PR group and mouse model. |
| Databáze: | OpenAIRE |
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