PMID- 32696071
OWN - NLM
STAT- MEDLINE
DCOM- 20210129
LR  - 20220102
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 70
IP  - 1
DP  - 2021 Jan
TI  - Human leukocyte antigen expression in paired primary lung tumors and brain 
      metastases in non-small cell lung cancer.
PG  - 215-219
LID - 10.1007/s00262-020-02677-7 [doi]
AB  - Loss of human leukocyte antigen (HLA) class 1 expression is a mechanism of tumor 
      immune escape and may contribute to resistance to immunotherapy. Patients with 
      non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors can 
      have discordant responses between brain metastases and extracranial sites of 
      disease. We sought to evaluate whether HLA class 1 expression was retained in 
      metastatic NSCLC. Patients with paired primary NSCLC and brain metastases were 
      identified from our institution's tissue registry. HLA class 1 cell membrane 
      expression on tumor cells was determined by immunohistochemistry. Tumors with 
      greater than the median of 10% HLA expression were considered positive. Agreement 
      statistics (kappa) were used to assess the congruence of HLA expression. 51 patients 
      with paired primary NSCLC and brain lesions were identified. The median HLA class 
      1 expression was 20% in the primary tumors (IQR 0-65%) and 10% in the brain 
      metastases (IQR 5-40%). 27 primary tumors and 24 brain metastases were positive 
      for HLA expression. There was disagreement in HLA positivity between paired 
      lesions in 11 patients (22%, 95% CI 12-35%) (kappa = 0.57, 95% CI 0.35-0.79) 
      (p = 0.0001). None of the patients received checkpoint inhibitors for treatment 
      of these lesions. The results show that while there is moderate agreement in HLA 
      class 1 expression between primary lung tumor and brain metastasis pairs, HLA 
      expression is incongruent in nearly one quarter of patients. Loss of antigen 
      presentation may represent one of the many potential mechanisms of discordant 
      responses to checkpoint inhibitor therapy.
FAU - Failing, Jarrett J
AU  - Failing JJ
AD  - Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First 
      Street SW, Rochester, MN, 55905, USA.
FAU - Aubry, Marie Christine
AU  - Aubry MC
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Mansfield, Aaron S
AU  - Mansfield AS
AUID- ORCID: 0000-0002-9483-6903
AD  - Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First 
      Street SW, Rochester, MN, 55905, USA. mansfield.aaron@mayo.edu.
LA  - eng
GR  - P30 CA015083/CA/NCI NIH HHS/United States
GR  - P30CA015083/Foundation for the National Institutes of Health/
PT  - Journal Article
DEP - 20200721
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigen Presentation/*immunology
MH  - Biomarkers, Tumor/immunology
MH  - Brain Neoplasms/*immunology
MH  - Carcinoma, Non-Small-Cell Lung/*immunology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Immunotherapy/methods
MH  - Lung Neoplasms/*immunology
MH  - Male
MH  - Middle Aged
PMC - PMC7854856
MID - NIHMS1613885
OTO - NOTNLM
OT  - Brain metastases
OT  - Human leukocyte antigen (HLA) class 1
OT  - Immunotherapy
OT  - Non-small cell lung cancer
COIS- Dr. Mansfield reports research support from Novartis, and Verily; remuneration to 
      his institution for participation on advisory boards for AbbVie, BMS, Astra 
      Zeneca and Genentech; travel support from Roche, and is a nonremunerated director 
      of the Mesothelioma Applied Research Foundation. Dr. Failing and Dr. Aubry report 
      no conflicts of interest.
EDAT- 2020/07/23 06:00
MHDA- 2021/01/30 06:00
PMCR- 2020/07/21
CRDT- 2020/07/23 06:00
PHST- 2020/05/13 00:00 [received]
PHST- 2020/07/17 00:00 [accepted]
PHST- 2020/07/23 06:00 [pubmed]
PHST- 2021/01/30 06:00 [medline]
PHST- 2020/07/23 06:00 [entrez]
PHST- 2020/07/21 00:00 [pmc-release]
AID - 10.1007/s00262-020-02677-7 [pii]
AID - 2677 [pii]
AID - 10.1007/s00262-020-02677-7 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2021 Jan;70(1):215-219. doi: 
      10.1007/s00262-020-02677-7. Epub 2020 Jul 21.