Table_1_Case Report: Circulating Myeloid-Derived Suppressive-Like Cells and Exhausted Immune Cells in Non-Small Cell Lung Cancer Patients Treated With Three Immune Checkpoint Inhibitors.docx

Immune checkpoint inhibition induced a great step forward in the treatment of non-small cell lung cancer patients. In cancer immune microenvironment many checkpoints were studied and their involvement could represent a mechanism of resistance to cancer immunotherapy. For this reason, the inhibition of multiple immune checkpoints is under development. However, myeloid-derived suppressor cells (MDSC) and exhausted immune cells could limit the efficacy of cancer immunotherapy. We analyzed the variation of circulating immune suppressive-like cell subsets and exhausted immune cells in three non-small cell lung cancer patients treated with the combination of anti-CTLA-4 plus anti-PD-1 plus anti-LAG-3 at T0 (baseline), T1 (after 2 months) and T2 (after 4 months). We also describe the clinical and radiological course of the disease during this treatment in all three patients. We observed both clinical differences and changes in the composition of immune suppressive-like cell subsets and exhausted immune cells between the patients receiving the same schedule of treatment with immune checkpoint inhibitors. The study on a wider patient population and experimental model design could help to clarify the kinetics of these cell subpopulations with the perspective to find new targets for treatment or new biomarkers for resistance to cancer immunotherapy.

免疫检查点抑制（immune checkpoint inhibition）疗法为非小细胞肺癌患者的治疗带来了重大突破。在肿瘤免疫微环境中，多种免疫检查点已被广泛研究，其介导的通路可能成为肿瘤免疫治疗耐药的潜在机制。基于此，多免疫检查点联合抑制疗法正处于研发阶段。然而，髓系来源抑制性细胞（myeloid-derived suppressor cells, MDSC）与耗竭性免疫细胞可能会限制肿瘤免疫治疗的疗效。本研究针对3例接受抗CTLA-4、抗PD-1与抗LAG-3联合治疗的非小细胞肺癌患者，分别在T0（基线期）、T1（治疗2个月后）与T2（治疗4个月后）三个时间点，分析了循环免疫抑制样细胞亚群与耗竭性免疫细胞的动态变化。同时，本研究还记录了全部3例患者在该治疗期间的临床与影像学病程变化。研究发现，即便接受相同方案的免疫检查点抑制剂治疗，不同患者间仍存在临床疗效差异，且其免疫抑制样细胞亚群与耗竭性免疫细胞的组成也会发生相应改变。未来可通过扩大患者队列规模、优化实验模型设计，进一步阐明这些细胞亚群的动态变化规律，以期为肿瘤免疫治疗找到全新的治疗靶点或耐药生物标志物。