Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment: Beyond immune evasion

Peixin Dong, Ying Xiong, Junming Yue, Sharon J.B. Hanley, Hidemichi Watari

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Although the role of PD-L1 in suppressing the anti-tumor immune response is extensively documented, recent discoveries indicate a distinct tumor-intrinsic role for PD-L1 in modulating epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC)-like phenotype, metastasis and resistance to therapy. In this review, we will focus on the newly discovered functions of PD-L1 in the regulation of cancer development, describe underlying molecular mechanisms responsible for PD-L1 upregulation and discuss current insights into novel components of PD-L1 signaling. Furthermore, we summarize our current understanding of the link between PD-L1 signaling and the EMT program as well as the CSC state. Tumor cell-intrinsic PD-L1 clearly contributes to cancer stemness, EMT, tumor invasion and chemoresistance in multiple tumor types. Conversely, activation of OCT4 signaling and upregulation of EMT inducer ZEB1 induce PD-L1 expression in cancer cells, thereby suggesting a possible immune evasion mechanism employed by cancer stem cells during metastasis. Our meta-analysis demonstrated that PD-L1 is co-amplified along with MYC, SOX2, N-cadherin and SNAI1 in the TCGA endometrial and ovarian cancer datasets. Further identification of immune-independent PD-L1 functions and characterization of crucial signaling events upstream or downstream of PD-L1 in diverse cancer types and specific cancer subtypes, would provide additional targets and new therapeutic approaches.

Original languageEnglish (US)
Article number386
JournalFrontiers in Oncology
Volume8
Issue numberSEP
DOIs
StatePublished - Sep 19 2018

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Immune Evasion
Epithelial-Mesenchymal Transition
Neoplasms
Neoplastic Stem Cells
Up-Regulation
Neoplasm Metastasis
Cadherins
Endometrial Neoplasms
Ovarian Neoplasms
Meta-Analysis
Phenotype

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment : Beyond immune evasion. / Dong, Peixin; Xiong, Ying; Yue, Junming; Hanley, Sharon J.B.; Watari, Hidemichi.

In: Frontiers in Oncology, Vol. 8, No. SEP, 386, 19.09.2018.

Research output: Contribution to journalReview article

Dong, Peixin ; Xiong, Ying ; Yue, Junming ; Hanley, Sharon J.B. ; Watari, Hidemichi. / Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment : Beyond immune evasion. In: Frontiers in Oncology. 2018 ; Vol. 8, No. SEP.
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