Zandberg Dan P, Hong Chang-Sook, Swartz Andrew, Hsieh Ronan, Anderson Jennifer, Ferris Robert L, Diergaarde Brenda, Whiteside Theresa L
UPMC Hillman Cancer Center, Pittsburgh, PA USA.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
BJC Rep. 2024;2(1):70. doi: 10.1038/s44276-024-00096-0. Epub 2024 Sep 11.
Biomarkers that effectively predict response to anti-PD-1 mAb therapy in cancer patients are an unmet need. We evaluated the utility of small extracellular vesicles (sEV) as biomarkers of response to immunotherapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.
Plasma sEV were isolated from 24 R/M HNSCC patients prior to immunotherapy initiation. sEV were separated by immune capture into T cell-derived CD3(+) and tumor-enriched CD3(-) subsets. Stimulatory and suppressive profiles of CD3(-) sEV were determined by on-bead flow cytometry. Differences were assessed using nonparametric tests. Multivariable Cox regression was used to evaluate the relationship with overall (OS) and progression free survival (PFS).
CD3(-)CD44v3(+) sEV represented the majority of plasma sEV; the T-cell-derived CD3(+) fraction was significantly smaller. High CD3(+) sEV was associated with better OS and PFS. Total CD3(-)CD44v3(+) sEV was not associated with outcome. However, suppressive and stimulatory profiles were associated with OS; the suppressive/stimulatory ratio was associated with best response. Exploration of individual proteins on CD3(-) sEV showed that high PD-L1 and high CTLA-4 were associated with better outcomes.
Evaluation of the T cell-derived-CD3(+) and tumor-enriched CD3(-) plasma sEV subsets indicated their potential utility as biomarkers of response to immunotherapy.
有效预测癌症患者抗PD-1单克隆抗体治疗反应的生物标志物仍未得到满足。我们评估了小细胞外囊泡（sEV）作为复发/转移性（R/M）头颈部鳞状细胞癌（HNSCC）患者免疫治疗反应生物标志物的效用。
在免疫治疗开始前，从24例R/M HNSCC患者中分离血浆sEV。通过免疫捕获将sEV分离为T细胞来源的CD3(+)和肿瘤富集的CD3(-)亚群。通过微珠流式细胞术确定CD3(-) sEV的刺激和抑制特征。使用非参数检验评估差异。多变量Cox回归用于评估与总生存期（OS）和无进展生存期（PFS）的关系。
CD3(-)CD44v3(+) sEV占血浆sEV的大部分；T细胞来源的CD3(+)部分明显较小。高CD3(+) sEV与更好的OS和PFS相关。总CD3(-)CD44v3(+) sEV与预后无关。然而，抑制和刺激特征与OS相关；抑制/刺激比与最佳反应相关。对CD3(-) sEV上单个蛋白质的探索表明，高PD-L1和高CTLA-4与更好的预后相关。
对T细胞来源的CD3(+)和肿瘤富集的CD3(-)血浆sEV亚群的评估表明它们作为免疫治疗反应生物标志物的潜在效用。
