Cancer Medicine (Apr 2023)

Comprehensive immunoprofile analysis of prognostic markers in pancreaticobiliary tract cancers

  • Ji Eun Kim,
  • Hyemin Kim,
  • Binnari Kim,
  • Hye Gyo Chung,
  • Hwe Hoon Chung,
  • Kyoung Mee Kim,
  • Seong Hyun Kim,
  • Woo Kyoung Jeong,
  • Young Kon Kim,
  • Ji Hye Min,
  • Jin Seok Heo,
  • In Woong Han,
  • Sang Hyun Shin,
  • Hee Chul Park,
  • Jeong Il Yu,
  • Joon Oh Park,
  • Seung Tae Kim,
  • Jung Yong Hong,
  • Se‐Hoon Lee,
  • Kwang Hyuck Lee,
  • Jong Kyun Lee,
  • Kyu Taek Lee,
  • Kee‐Taek Jang,
  • Joo Kyung Park

DOI
https://doi.org/10.1002/cam4.5530
Journal volume & issue
Vol. 12, no. 7
pp. 7748 – 7761

Abstract

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Abstract Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T‐cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD‐1, PD‐L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD‐L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD‐1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD‐1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD‐L1 (p < 0.0001), PD‐1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD‐1, and PD‐L1 might have prognostic values in patients with pancreaticobiliary tract cancers.

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