The prognostic value of tumour-infiltrating lymphocytes (TILs) in pancreatic cancer: A systematic review and meta-analysis

Abstract

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.