下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:The Density of CD8(+) Tumor-infiltrating Lymphocytes Correlated With Akt Activation and Ki-67 Index in Canine Soft Tissue Sarcoma.
PI3K/Akt 通路激活可能影响犬 STS 肿瘤微环境中 CD8⁺ T 细胞的浸润。
背景/目的:磷脂酰肌醇3激酶(PI3K)/Akt通路激活可能参与犬软组织肉瘤发生,并可作为预后指标。本研究探讨肿瘤细胞PI3K/Akt活化与TIL(肿瘤浸润淋巴细胞)的关系。方法:对59份软组织肉瘤标本进行免疫组化,评估CD3、CD8阳性T细胞、CD20阳性B细胞及FOXP3阳性调节性T细胞密度。结果:81.3%的标本有瘤内TIL,其中CD3和CD8细胞较多,而CD20和FOXP3细胞较少。多变量分析显示不同TIL亚群数量间高度相关。TIL密度与临床病理特征或肿瘤分级无关;但CD8细胞数量与PI3K/Akt活化正相关,Ki-67指数较高的标本中CD3、CD8及CD20细胞也更多。结论:PI3K/Akt通路活化可能影响犬软组织肉瘤微环境中的CD8细胞浸润,需更大样本的前瞻性研究验证。
BACKGROUND/AIM: The activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway has been implicated in canine soft tissue sarcoma (STS) and may serve as a prognostic marker. This study investigated the correlation between PI3K/Akt activation in tumor cells and tumor-infiltrating lymphocytes (TILs). MATERIALS AND METHODS: A total of 59 STS samples were labeled via immunohistochemistry to calculate the density of TILs, including CD3+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ regulatory T cells. RESULTS: Forty-eight samples (81.3%) had intra-tumoral TILs with a high density of CD3+ T cells (mean: 283.3 cells/mm 2 ) and CD8+ T cells (mean: 134.8 cells/mm 2 ). Conversely, CD20+ B cells (mean: 73.6 cells/mm 2 ) and FOXP3+ regulatory T cells (mean: 9.2 cells/mm 2 ) were scarce. The abundance of CD3+/CD8+, CD3+/CD20+, and CD8+/CD20+ TILs were highly correlated in multivariate analyses (r=0.895, 0.946, and 0.856, respectively). Nonetheless, TIL density was unrelated to clinicopathological parameters (sex, age, tumor location, breed) and tumor grade. The abundance of CD8+ T cells was positively correlated with the activation of PI3K/Akt, indicating that samples with high levels of phospho-Akt and phospho-S6 tend to have a higher CD8+ T cell density (p=0.0032 and 0.0218, respectively). Furthermore, TIL density was correlated with the Ki-67 index, a tumor proliferation and growth marker. Samples with a high Ki-67 index had a significantly higher abundance of CD3+ T cells, CD8+ T cells, and CD20+ B cells (p=0.0392, 0.0254, 0.0380, respectively). CONCLUSION: PI3K/Akt pathway activation may influence the infiltration of CD8+ T cells within the tumor microenvironment in canine STS. Prospective studies involving a higher number of cases are warranted to confirm these findings.
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