PMID- 37149969
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230522
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 33
DP  - 2023 Jul
TI  - High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to 
      Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma.
PG  - 101678
LID - S1936-5233(23)00064-5 [pii]
LID - 10.1016/j.tranon.2023.101678 [doi]
LID - 101678
AB  - BACKGROUND: HLA-DR is expressed in epithelial and several types of tumor cells. 
      However, the correlation between tumor-expressed HLA-DR (teHLA-DR) and patient 
      outcome as well as its regulation on the tumor microenvironment (TME) of 
      laryngeal squamous cell carcinoma (LSCC) are yet to be elucidated. METHODS: 
      Hematoxylin and eosin (HE) staining were performed to define the tumor nest and 
      stroma of LSCC tissue microarrays. teHLA-DR tumor cell, CD4(+) and CD8(+) 
      tumor-infiltrating T lymphocytes (TITLs) were obtained and analyzed through 
      double-labeling immunofluorescence and immunohistochemical staining. The 
      recurrence-free (RFS) and overall survival (OS) curves were plotted using the 
      Kaplan-Meier method and tested by the log-rank test method. Expression of 
      teHLA-DR(+) tumor cells and infiltration of T lymphocytes and their corresponding 
      subgroups were analyzed by flow cytometry using fresh LSCC tissue samples. 
      RESULTS: Our research discovered elevated expressions of multiple MHC-II-related 
      genes in tumor compared to the adjacent normal tissue samples of LSCC patients. 
      We also found that patients in the teHLA-DR high-expression group 
      (teHLA-DR(high)) tend to have less tumor recurrence and better survival outcomes 
      compared to those in the teHLA-DR(low) group. Intriguingly, teHLA-DR(+) tumor 
      cells had significantly higher PD-L1 and PD-L2 expression and their TME showed 
      increased infiltrated T lymphocytes (TITLs). Flow cytometry analysis and IHC 
      staining indicated that CD4(+) TITLs but not CD3(+) total TITLs or CD8(+) TITLs 
      were significantly enriched in teHLA-DR(+) tumors. CONCLUSIONS: teHLA-DR may be a 
      predictive marker for favorable prognosis and response to anti-PD-1/PD-L1 therapy 
      of LSCC, possibly due to the increased CD4(+) TITLs in the TME.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Heng, Yu
AU  - Heng Y
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan 
      University, Shanghai 200031, China.
FAU - Zhu, Xiaoke
AU  - Zhu X
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan 
      University, Shanghai 200031, China.
FAU - Wu, Qian
AU  - Wu Q
AD  - Shanghai Institute of Immunology, Department of Immunology and Microbiology, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Lin, Hanqing
AU  - Lin H
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan 
      University, Shanghai 200031, China.
FAU - Ding, Xuping
AU  - Ding X
AD  - Shanghai Institute of Immunology, Department of Immunology and Microbiology, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Tao, Lei
AU  - Tao L
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan 
      University, Shanghai 200031, China. Electronic address: lei.tao@fdeent.org.
FAU - Lu, Liming
AU  - Lu L
AD  - Shanghai Institute of Immunology, Department of Immunology and Microbiology, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. 
      Electronic address: youlanda2009@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230505
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC10192652
OTO - NOTNLM
OT  - Laryngeal squamous cell carcinoma
OT  - PD-L1
OT  - Personalized medicine
OT  - Tumor-expressed HLA-DR
OT  - Tumor-infiltrating T lymphocyte
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/08 00:41
MHDA- 2023/05/08 00:42
PMCR- 2023/05/05
CRDT- 2023/05/07 18:03
PHST- 2023/01/04 00:00 [received]
PHST- 2023/04/12 00:00 [revised]
PHST- 2023/04/14 00:00 [accepted]
PHST- 2023/05/08 00:42 [medline]
PHST- 2023/05/08 00:41 [pubmed]
PHST- 2023/05/07 18:03 [entrez]
PHST- 2023/05/05 00:00 [pmc-release]
AID - S1936-5233(23)00064-5 [pii]
AID - 101678 [pii]
AID - 10.1016/j.tranon.2023.101678 [doi]
PST - ppublish
SO  - Transl Oncol. 2023 Jul;33:101678. doi: 10.1016/j.tranon.2023.101678. Epub 2023 
      May 5.