Tumour-infiltrating Lymphocytes and Radiation Therapy in Rectal Cancer: Systematic Review and Meta-analysis

IF 3 3区医学 Q2 ONCOLOGY Clinical oncology Pub Date : 2025-03-01 Epub Date: 2024-12-20 DOI:10.1016/j.clon.2024.103742

J. Klein , W.T. Tran , S. Viswanathan , R. Salgado , P. Poortmans , M. Machiels

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Abstract

Aim

Tumour-infiltrating lymphocytes (TILs) represent a promising cancer biomarker. Different TILs, including CD8+, CD4+, CD3+, and FOXP3+, have been associated with clinical outcomes. However, data are lacking regarding the value of TILs for patients receiving radiation therapy (RT). We conducted a systemic review and meta-analysis of available data evaluating TILs for patients receiving curative-intent therapy including RT.

Materials and Methods

Eligible studies presented a defined cohort of patients who all received curative-intent therapy, including RT, and also reported the relationship between any TIL score and either tumour response or survival outcomes. After comprehensive search of online databases (PubMed, EMBASE, Cochrane, and Web of Science), 2 authors conducted title, abstract, and whole-text review for quality and risk of bias following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data from publications that met quality criteria were grouped via (1) TIL analysed, (2) pre- or post-RT TIL assessment, and (3) clinical outcome measured.

Results

Initial search yielded 669 unique studies. Thirty-one studies met quality criteria, of which 20 studied rectal cancer (RC), 4 oesophageal, 3 pancreas, 2 lung, cervical/uterine 1 each. We conducted systematic review and meta-analysis of the RC publications. All except 2 were single-institutional cohort studies. After meta-analysis, the pre-RT epithelial CD8+ (p = 0.04) and stromal FOXP3+ (p = 0.01) counts were associated with survival without disease, while pre-RT epithelial (p = 0.02) and stromal (p = 0.001) FOXP3+ TILs were associated with overall survival. On post-RT analysis, epithelial (p = .04) and stromal (p = 0.02) CD8+ TILs were associated with survival without disease and epithelial CD8+ TILs were associated with overall survival (p = 0.01).Preoperative CD8+ and FOXP3+ TILs were generally associated with tumour response to RT, but meta-analysis was not conducted due to heterogeneity of response measurement techniques.

Conclusion

TILs represent a useful parameter for tumour response and survival outcomes for patients receiving curative-intent therapy, including RT for RC. Future work should aim to standardise TIL measurement and quantification methods and to develop protocols to clarify clinical application of these findings.

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肿瘤浸润淋巴细胞和放疗在直肠癌中的作用：系统回顾和荟萃分析。

目的：肿瘤浸润淋巴细胞（肿瘤浸润淋巴细胞）是一种很有前景的肿瘤生物标志物。不同的TILs，包括CD8+、CD4+、CD3+和FOXP3+，与临床结果相关。然而，关于TILs对接受放射治疗（RT）的患者的价值，缺乏数据。我们对接受治疗目的治疗（包括RT）的患者的TIL进行了系统评价和荟萃分析。材料和方法：符合条件的研究提出了一组接受治疗目的治疗（包括RT）的患者，并报告了TIL评分与肿瘤反应或生存结果之间的关系。在对在线数据库（PubMed、EMBASE、Cochrane和Web of Science）进行全面检索后，2位作者按照系统评价和荟萃分析首选报告项目（PRISMA）指南对标题、摘要和全文进行了质量和偏倚风险评价。符合质量标准的出版物数据通过(1)TIL分析，(2)rt前或rt后TIL评估和(3)临床结果测量进行分组。结果：最初的搜索产生了669个独特的研究。31项研究符合质量标准，其中直肠癌20项，食管癌4项，胰腺癌3项，肺癌2项，宫颈癌/子宫癌各1项。我们对RC出版物进行了系统回顾和荟萃分析。除2项外，其余均为单机构队列研究。经荟萃分析，rt前上皮CD8+ (p = 0.04)和基质FOXP3+ (p = 0.01)计数与无病生存率相关，而rt前上皮（p = 0.02）和基质（p = 0.001） FOXP3+ TILs与总生存率相关。在rt后分析中，上皮（p = 0.04）和间质（p = 0.02） CD8+ TILs与无疾病生存相关，上皮CD8+ TILs与总生存相关（p = 0.01）。术前CD8+和FOXP3+ TILs通常与肿瘤对RT的反应相关，但由于反应测量技术的异质性，未进行meta分析。结论：TILs代表了接受治疗意图治疗的患者的肿瘤反应和生存结果的有用参数，包括RC的RT。未来的工作应旨在标准化TIL测量和量化方法，并制定方案以阐明这些发现的临床应用。

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来源期刊

Clinical oncology 医学-肿瘤学

CiteScore

5.20

自引率

8.80%

发文量

332

审稿时长

40 days

期刊介绍： Clinical Oncology is an International cancer journal covering all aspects of the clinical management of cancer patients, reflecting a multidisciplinary approach to therapy. Papers, editorials and reviews are published on all types of malignant disease embracing, pathology, diagnosis and treatment, including radiotherapy, chemotherapy, surgery, combined modality treatment and palliative care. Research and review papers covering epidemiology, radiobiology, radiation physics, tumour biology, and immunology are also published, together with letters to the editor, case reports and book reviews.