PMID- 35210813
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220502
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 15
DP  - 2022
TI  - Tumor-Infiltrating PD-L1+ Neutrophils Induced by GM-CSF Suppress T Cell Function 
      in Laryngeal Squamous Cell Carcinoma and Predict Unfavorable Prognosis.
PG  - 1079-1097
LID - 10.2147/JIR.S347777 [doi]
AB  - PURPOSE: Chronic inflammation contributes to tumor initiation, progression, and 
      immune escape. Neutrophils are the major component of inflammatory response and 
      participate in the tumorigenesis process. However, compared to other immune cells 
      in the tumor microenvironment of laryngeal squamous cell carcinoma (LSCC), 
      neutrophils, especially the tumor-associated neutrophils (TANs), have not yet 
      been comprehensively explored. The mechanism for regulating the crosstalk between 
      TANs and tumor cells still remains unclear. MATERIALS AND METHODS: The 
      distribution profiles and phenotypic features of neutrophils and other 
      inflammatory immune cell populations from a large LSCC patient cohort were 
      systemically analyzed. Co-culturing of peripheral blood associated neutrophils 
      (PANs) and TANs with PBMCs was performed, and the immunosuppression effect on 
      T-cells was examined. RESULTS: LSCC microenvironment is highly inflammatory with 
      remarkable TANs infiltration, which is often associated with unfavorable 
      prognosis and advanced clinical stage. We find that TANs in LSCC display 
      morphologically immature and lower apoptosis, exhibit distinctively 
      immunosuppressive phenotype of high PD-L1, and suppress CD8(+) T lymphocytes 
      proliferation and activation. We subsequently discover that PD-L1(+)TANs induced 
      by LSCC-derived GM-CSF potently impair CD8(+) T-cells proliferation and cytokines 
      production function, which are partially blocked by a PD-L1-neutralizing 
      antibody. Clinical data further support GM-CSF as an unfavorable prognostic 
      biomarker and reveal a potential association with inflammatory immune cell 
      infiltration, in particular neutrophils. CONCLUSION: Tumor-infiltrating PD-L1+ 
      neutrophils induced by LSCC-derived GM-CSF suppress T cell proliferation and 
      activation in the inflammatory microenvironment of LSCC and predict unfavorable 
      prognosis. These TANs cripple antitumor T cell immunity and promote tumor 
      progression. Our findings provide a basis for targeting PD-L1+TANs or GM-CSF as a 
      new immunotherapeutic strategy for LSCC.
CI  - (c) 2022 Tang et al.
FAU - Tang, Di
AU  - Tang D
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Zhang, Duo
AU  - Zhang D
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Heng, Yu
AU  - Heng Y
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Zhu, Xiao-Ke
AU  - Zhu XK
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Lin, Han-Qing
AU  - Lin HQ
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Zhou, Jian
AU  - Zhou J
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Tao, Lei
AU  - Tao L
AD  - Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Lu, Li-Ming
AU  - Lu LM
AD  - Shanghai Institute of Immunology, Shanghai Jiaotong University School of 
      Medicine, Shanghai, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20220216
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8859980
OTO - NOTNLM
OT  - GM-CSF
OT  - LSCC
OT  - PD-L1
OT  - TANs
OT  - granulocyte-macrophage colony stimulating factor
OT  - immune suppression
OT  - inflammatory microenvironment
OT  - laryngeal squamous cell carcinoma
OT  - tumor-associated neutrophils
COIS- The authors declare no conflict of interest in this work.
EDAT- 2022/02/26 06:00
MHDA- 2022/02/26 06:01
PMCR- 2022/02/16
CRDT- 2022/02/25 05:36
PHST- 2021/11/11 00:00 [received]
PHST- 2022/02/02 00:00 [accepted]
PHST- 2022/02/25 05:36 [entrez]
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/02/26 06:01 [medline]
PHST- 2022/02/16 00:00 [pmc-release]
AID - 347777 [pii]
AID - 10.2147/JIR.S347777 [doi]
PST - epublish
SO  - J Inflamm Res. 2022 Feb 16;15:1079-1097. doi: 10.2147/JIR.S347777. eCollection 
      2022.