Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
Medical Oncology, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
Int J Cancer. 2020 Jul 15;147(2):554-564. doi: 10.1002/ijc.32893. Epub 2020 Feb 26.
We investigated the potential of tumor-infiltrating immune cells (ICs) as predictive or prognostic biomarkers for cervical cancer patients. In total, 38 patients treated with (chemo)radiotherapy and subsequent surgery were included in the current study. This unique treatment schedule makes it possible to analyze IC markers in pretreatment and posttreatment tissue specimens and their changes during treatment. IC markers for T cells (CD3, CD4, CD8 and FoxP3), macrophages (CD68 and CD163) and B cells (CD20), as well as IL33 and PD-L1, were retrospectively analyzed via immunohistochemistry. Patients were grouped in the low score or high score group based on the amount of positive cells on immunohistochemistry. Correlations to pathological complete response (pCR), cause-specific survival (CSS) and metastasis development during follow-up were evaluated. In analysis of pretreatment biopsies, significantly more pCR was seen for patients with CD8 = CD3, CD8 ≥ CD4, positive IL33 tumor cell (TC) scores, IL33 IC < TC and PD-L1 TC ≥5%. Besides patients with high CD8 scores, also patients with CD8 ≥ CD4, CD163 ≥ CD68 or PD-L1 IC ≥5% had better CSS. In the analysis of posttreatment specimens, less pCR was observed for patients with high CD8 or CD163 scores. Patients with decreasing CD8 or CD163 scores between pretreatment and posttreatment samples showed more pCR, whereas those with increasing CD8 or decreasing IL33 IC scores showed a worse CSS. Meanwhile, patients with an increasing CD3 score or stable/increasing PD-L1 IC score showed more metastasis during follow-up. In this way, the intratumoral IC landscape is a promising tool for prediction of outcome and response to (chemo)radiotherapy.
我们研究了肿瘤浸润免疫细胞（ICs）作为预测或预后生物标志物在宫颈癌患者中的潜力。共有 38 名接受（放）化疗和随后手术治疗的患者纳入本研究。这种独特的治疗方案使得在治疗前和治疗后组织标本中分析 IC 标志物及其在治疗过程中的变化成为可能。通过免疫组织化学法回顾性分析了 T 细胞（CD3、CD4、CD8 和 FoxP3）、巨噬细胞（CD68 和 CD163）和 B 细胞（CD20）的 IC 标志物以及 IL33 和 PD-L1。根据免疫组化中阳性细胞的数量将患者分为低评分组或高评分组。评估了与病理完全缓解（pCR）、特异性生存（CSS）和随访期间转移发展的相关性。在分析治疗前活检时，CD8 = CD3、CD8≥CD4、IL33 肿瘤细胞（TC）评分阳性、IL33 IC<TC 和 PD-L1 TC≥5%的患者中 pCR 显著更高。除了 CD8 评分高的患者外，CD8≥CD4、CD163≥CD68 或 PD-L1 IC≥5%的患者 CSS 更好。在分析治疗后标本时，CD8 或 CD163 评分高的患者 pCR 较低。治疗前和治疗后标本之间 CD8 或 CD163 评分降低的患者 pCR 更高，而 CD8 或 IL33 IC 评分升高的患者 CSS 更差。同时，CD3 评分增加或 PD-L1 IC 评分稳定/增加的患者在随访期间发生更多转移。这样，肿瘤内 IC 景观是预测治疗结果和对（放）化疗反应的有前途的工具。
