Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy.
Elaine Lai-Han LeungRun-Ze LiXing-Xing FanLily Yan WangYan WangZebo JiangJumin HuangHu-Dan PanYue FanHongmei XuFeng WangHaopeng RuiPiu WongHermi SumatohMichael FehlingsAlessandra NardinPaul GavineLongen ZhouYa-Bing CaoLiang LiuPublished in: Nature communications (2023)
Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8 + and of CD8 + CD101 hi TIM3 + (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8 + T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.
Keyphrases
- peripheral blood
- free survival
- patients undergoing
- single cell
- poor prognosis
- small cell lung cancer
- cross sectional
- small molecule
- cell therapy
- stem cells
- genome wide
- high throughput
- dna methylation
- bone marrow
- smoking cessation
- replacement therapy
- mesenchymal stem cells
- transcription factor
- long non coding rna
- combination therapy
- brain metastases