Matthew R Trendowski, Donovan Watza, Christine M Lusk, Fulvio Lonardo, Valerie Ratliff, Angela S Wenzlaff, Hirva Mamdani, Christine Neslund-Dudas, Julie L Boerner, Ann G Schwartz, Heather M Gibson
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引用次数: 0
摘要
背景：非裔美国人的肺癌发病率和死亡率均高于非西班牙裔白人，但有关免疫反应差异的研究却很少。因此，我们根据 PD-L1 或三级淋巴结构（TLS）状态比较了非裔美国人和非西班牙裔白人中确诊为非小细胞肺癌（NSCLC）的肿瘤微环境成分，以确定与转化相关的差异：我们利用INHALE研究中的280名NSCLC患者（非西班牙裔白人：n=155；非裔美国人：n=125），对PD-L1肿瘤比例评分进行了评估（结果：非裔美国人的肿瘤比例评分更高，而非裔美国人的肿瘤比例评分更低）：与非西班牙裔白人相比，非裔美国人的肿瘤微环境中浆细胞特征的比例更高。此外，非裔美国人 PD-L1 阳性样本的基因表达模式表明，在调整年龄、性别、包年、分期和组织学后，这些肿瘤含有更多的 γδ T 细胞和静息树突状细胞，而 CD8+ T 细胞较少。对两个患者群体的 B 细胞/浆细胞相关基因的差异表达进行调查后发现，两个免疫球蛋白基因（IGKV2-29 和 IGLL5）与非裔美国人的死亡风险降低有关：在首次基于 PD-L1 表达或 TLS 状态对肺癌肿瘤微环境成分进行的已知种族分层分析中，发现了免疫细胞组成和转录组特征的差异，这些差异可能具有治疗意义：影响：未来对肿瘤微环境中种族差异的研究可能有助于指导免疫疗法的使用。
Evaluation of the Immune Response within the Tumor Microenvironment in African American and Non-Hispanic White Patients with Non-Small Cell Lung Cancer.
Background: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance.
Methods: Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes.
Results: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PDL1-positive samples suggest that these tumors contained greater numbers of γδ T cells and resting dendritic cells, along with fewer CD8+ T cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B cell/plasma cell-related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans.
Conclusions: In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PDL1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications.
Impact: Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.
期刊介绍：
Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.
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