Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment
Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment
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DOI：
10.1002/ijc.32893
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发表时间：
2020-02-26
影响因子：
6.4
通讯作者：
Denys, Hannelore
中科院分区：
文献类型：
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作者：
Lippens, Lien;Van Bockstal, Mieke;Denys, Hannelore
我们研究了肿瘤浸润免疫细胞（IC）作为宫颈癌患者预测或预后生物标志物的潜力。本研究共纳入38例接受（化疗）放疗和后续手术治疗的患者。这种独特的治疗方案使分析治疗前和治疗后组织标本中的IC标志物及其在治疗期间的变化成为可能。通过免疫组织化学回顾性分析T细胞（CD 3、CD 4、CD 8和FoxP 3）、巨噬细胞（CD 68和CD 163）和B细胞（CD 20）的IC标志物以及IL 33和PD-L1。根据免疫组化阳性细胞的数量将患者分为低分或高分组。在随访期间评估与病理学完全缓解（pCR）、病因特异性生存（CSS）和转移发展的相关性。在预处理活检的分析中，对于具有CD 8 = CD 3、CD 8>= CD 4、阳性IL 33肿瘤细胞（TC）评分、IL 33 IC = 5%的患者，观察到显著更多的pCR< TC and PD-L1 TC >。除CD 8评分高的患者外，CD 8>= CD 4、CD 163>= CD 68或PD-L1 IC >= 5%的患者CSS也较好。在治疗后标本的分析中，观察到CD 8或CD 163评分高的患者pCR较少。治疗前和治疗后样本之间CD 8或CD 163评分降低的患者显示更多的pCR，而CD 8或IL 33 IC评分升高或降低的患者显示更差的CSS。同时，CD 3评分增加或PD-L1 IC评分稳定/增加的患者在随访期间显示更多转移。通过这种方式，肿瘤内IC景观是预测结果和对（化疗）放疗反应的有前途的工具。
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.