CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.
Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.
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在这项工作中，我们发现 PDAC 中浸润性 CD3+和 CD8+淋巴细胞及个体炎症反应存在显著异质性。未来的机制研究应探索针对肿瘤微环境中免疫和炎症成分的个性化治疗策略。
胰腺导管腺癌（PDAC）具有异质性肿瘤微环境，相对缺乏浸润免疫细胞。我们旨在对未经治疗的患者队列中浸润性CD3+和CD8+淋巴细胞进行定量评估，并评估其与总生存期和微环境炎症蛋白的关联。
组织微阵列经免疫组化染色检测CD3+和CD8+淋巴细胞，并使用QuPath进行定量评估。通过多重酶联免疫吸附测定 panel 对匹配的肿瘤和组织样本中的炎症相关蛋白水平进行定量。
我们的研究结果显示，与non-PDAC组织相比，PDAC中CD3+和CD8+淋巴细胞群体均显著增加，但在比较PDAC与IPMN中的CD8+百分比时除外（p = 0.5012）。定量评估为CD3+低肿瘤（下50%）的患者生存期较短（中位273天），而CD3+高肿瘤（上50%）的中位OS为642.5天（p = 0.2184）。定量评估为CD8+低肿瘤的患者生存期显著较短（中位240天），而CD8+高肿瘤的中位OS为1059天（p = 0.0003）。在炎症检测中评估的41种蛋白质中，较高水平的IL-1B和IL-2与CD3+浸润减少显著相关（分别为r = -0.3704，p = 0.0187和r = -0.4275，p = 0.0074）。较高水平的IL-1B也与CD8+浸润减少显著相关（r = -0.4299，p = 0.0045），但IL-2则不然（r = -0.0078，p = 0.9616）。炎症分析物的主成分分析显示PDAC中存在多样的炎症反应。
Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.
Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.
Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.
In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
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