Abstract

Background

Pancreatic cancer (PC) contributes to over 7 % of all cancer related deaths worldwide with a relative 5-year survival of less than 8 %. High levels of tumor-infiltrating lymphocytes (TILs) are associated with improved survival in many cancer types. Examining the impact of TILs on survival in PC could provide better prognostication and help clinicians tailor therapy for patients.

Methods

A systematic search based on the PICO-process was conducted on PubMed, Embase, The Cochrane Library and Web of Science. Outcome of interest was overall survival (OS). Studies examining high vs. low levels of TILs in pancreatic tumor tissue and its impact on OS was included. Following data extraction a random-effects model meta-analysis was conducted on the reported outcome with corresponding lymphocyte subset. The Newcastle-Ottowa Scale was used for study quality assessment.

Results

In total, 43 studies were included in the systematic review and 40 were eligible for meta-analysis. A time-to-event meta-analysis on the different lymphocyte subtypes revealed, that high vs. low infiltration of CD3⁺ T and CD8⁺ T cells was significantly associated with improved OS (HR = 0.59, 95 % CI: 0.51 - 0.68, I²: 0 % and HR = 0.61, 95 % CI: 0.57 – 0.67, I²: 0 %, respectively). High infiltration of FoxP3⁺ T cells was associated with decreased OS (HR = 1.41, 95 % CI: 1.15 – 1.73, I²: 85 %). The prevalence of CD4⁺ and CD20⁺ lymphocytes in pancreatic tumor tissue was not significantly associated with increased OS (HR = 0.87, 95 % CI: 0.65 - 1.17, I²: 80 % and HR = 0.86, 95 % CI: 0.54 – 1.35, I²: 66 %, correspondingly).

Conclusion

High infiltration of CD3⁺ and CD8⁺ lymphocytes is associated with improved OS among patients with resected PC, whereas high infiltration of FoxP3⁺ T cells is associated with decreased OS. CD4⁺ and CD20⁺ lymphocytes did not have a significant impact on OS. Based on these findings, staining for TILs, especially CD3⁺, CD8⁺ and FoxP3⁺ T cells, might be an important tool for future assessment of patient survival and prognosis, as well as for tailored oncological therapy.

Clinical trial identification

CRD42019134744.

Legal entity responsible for the study

The authors.

Funding

Center for Surgical Science.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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8P肿瘤浸润淋巴细胞（TILs）在胰腺癌中的预后价值：系统评价和荟萃分析

抽象的

背景

胰腺癌（PC）占全世界所有癌症相关死亡的7％以上，相对5年生存率不到8％。高水平的肿瘤浸润淋巴细胞（TIL）与许多癌症类型的存活率提高有关。检查TIL对PC生存的影响可以提供更好的预后，并帮助临床医生为患者量身定制治疗方案。

方法

在PubMed，Embase，Cochrane图书馆和Web of Science上进行了基于PICO程序的系统搜索。感兴趣的结果是总体生存率（OS）。包括检查胰腺肿瘤组织中TIL的高水平和低水平及其对OS的影响的研究。数据提取后，对报告的结果与相应的淋巴细胞亚群进行随机效应模型荟萃分析。纽卡斯尔-奥托瓦量表用于研究质量评估。

结果

共有43项研究纳入系统评价，其中40项符合条件进行了荟萃分析。对不同淋巴细胞亚型的事件后荟萃分析显示，CD3 ⁺ T和CD8 ⁺ T细胞的高浸润与低浸润与OS改善显着相关（HR = 0.59，95％CI：0.51-0.68， I ²：0％，HR = 0.61，95％CI：0.57 – 0.67，I ²：0％）。FoxP3 ⁺ T细胞的高度浸润与OS降低有关（HR = 1.41，95％CI：1.15-1.73，I ²：85％）。CD4 ⁺和CD20 ⁺的患病率胰腺肿瘤组织中的淋巴细胞与OS升高无明显相关性（HR = 0.87，95％CI：0.65-1.17，I ²：80％，HR = 0.86，95％CI：0.54 – 1.35，I ²：66％，分别）。

结论

CD3 ⁺和CD8 ⁺淋巴细胞的高浸润与PC切除患者的OS改善相关，而FoxP3 ⁺ T细胞的高浸润与OS降低相关。CD4 ⁺和CD20 ⁺淋巴细胞对OS无明显影响。基于这些发现，对TILs染色，尤其是CD3 ⁺，CD8 ⁺和FoxP3 ⁺ T细胞，可能是将来评估患者生存和预后以及进行专门的肿瘤治疗的重要工具。

临床试验鉴定

CRD42019134744。

负责研究的法人实体

作者。

资金

外科科学中心。

揭露

所有作者均声明没有利益冲突。