PMID- 34012784
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220423
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 10
IP  - 4
DP  - 2021 Apr
TI  - Identification of PD-1 ligands: PD-L1 and PD-L2 on macrophages in lung cancer 
      milieu by flow cytometry.
PG  - 1679-1689
LID - 10.21037/tlcr-20-1103 [doi]
AB  - BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) remains 
      unexpected and in some patients the resistance to anti-programmed death-1 
      (anti-PD-1) and anti-programmed death ligand 1 (anti-PD-L1) agents is observed. 
      One of possible explanation may be PD-L2 activity. PD-1 ligands: PD-L1 and PD-L2 
      are present on cancer cells but also, not without significance, on alveolar 
      macrophages (AMs) contributing to immune-suppression in the tumor 
      microenvironment. The aim of this study was to analyse PD-L2, PD-L1 expression on 
      AMs in bronchoalveolar lavage fluid (BALF) in relation to PD-1 positive T 
      lymphocytes. METHODS: Seventeen patients with lung cancer were investigated. BALF 
      cells from the lung with cancer (clBALF) and from the opposite "healthy" lung 
      (hlBALF) and peripheral blood (PB) lymphocytes were investigated. Flow cytometry 
      method was used. RESULTS: We found that 100% of CD68+ AMs from the clBALF were 
      PD-L1 and PD-L2-positive. Unexpectedly, fluorescence minus one (FMO) PD-L1 and 
      PD-L2 stained controls and isotype controls also showed strong autofluorescence. 
      The hlBALF AMs exhibited a similar PD-L1 and PD-L2 autofluorescence. The median 
      proportion of PD-1+ T lymphocytes was higher in the clBALF than the hlBALF and PB 
      (28.9 vs. 23.4% vs. 15.6%, P=0.0281). CONCLUSIONS: We discussed the opportunities 
      of exploring the PD-1-PD-L1/PD-L2 pathway in the lung cancer environment, which 
      may help to find new potential biomarkers for immunotherapy. We concluded that 
      precise identification by flow cytometry of macrophages in the BALF is possible, 
      but our study showed that the autofluorescence of macrophages did not allow to 
      assess a real expression of PD-L2 as well as PD-L1 on AMs.
CI  - 2021 Translational Lung Cancer Research. All rights reserved.
FAU - Kwiecien, Iwona
AU  - Kwiecien I
AD  - Military Institute of Medicine, Department of Internal Medicine and Hematology, 
      Laboratory of Hematology and Flow Cytometry, Warsaw, Poland.
FAU - Rutkowska, Elzbieta
AU  - Rutkowska E
AD  - Military Institute of Medicine, Department of Internal Medicine and Hematology, 
      Laboratory of Hematology and Flow Cytometry, Warsaw, Poland.
FAU - Polubiec-Kownacka, Malgorzata
AU  - Polubiec-Kownacka M
AD  - Institute of Tuberculosis and Lung Diseases, Department of Surgery, Warsaw, 
      Poland.
FAU - Raniszewska, Agata
AU  - Raniszewska A
AD  - Military Institute of Medicine, Department of Internal Medicine and Hematology, 
      Laboratory of Hematology and Flow Cytometry, Warsaw, Poland.
FAU - Rzepecki, Piotr
AU  - Rzepecki P
AD  - Department of Internal Medicine and Hematology, Military Institute of Medicine, 
      Warsaw, Poland.
FAU - Domagala-Kulawik, Joanna
AU  - Domagala-Kulawik J
AD  - Medical University of Warsaw Department of Internal Medicine, Pulmonary Diseases 
      and Allergy, Warsaw, Poland.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC8107752
OTO - NOTNLM
OT  - Macrophages
OT  - PD-L1
OT  - PD-L2
OT  - bronchoalveolar lavage fluid (BALF)
OT  - lung cancer microenvironment
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tlcr-20-1103). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/05/21 06:00
MHDA- 2021/05/21 06:01
PMCR- 2021/04/01
CRDT- 2021/05/20 06:44
PHST- 2021/05/20 06:44 [entrez]
PHST- 2021/05/21 06:00 [pubmed]
PHST- 2021/05/21 06:01 [medline]
PHST- 2021/04/01 00:00 [pmc-release]
AID - tlcr-10-04-1679 [pii]
AID - 10.21037/tlcr-20-1103 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2021 Apr;10(4):1679-1689. doi: 10.21037/tlcr-20-1103.