Human leukocyte antigen expression in paired primary lung tumors and brain metastases in non-small cell lung cancer
- 21 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 70 (1), 215-219
- https://doi.org/10.1007/s00262-020-02677-7
Abstract
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 (κ) 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%) (κ = 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.Keywords
Funding Information
- Foundation for the National Institutes of Health (P30CA015083)
This publication has 12 references indexed in Scilit:
- Durability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab.Journal of Clinical Oncology, 2018
- The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responsesCurrent Opinion in Immunology, 2018
- Contraction of T cell richness in lung cancer brain metastasesScientific Reports, 2018
- HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escapeOncotarget, 2017
- Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung CancerCancer Discovery, 2017
- Allele-Specific HLA Loss and Immune Escape in Lung Cancer EvolutionCell, 2017
- Cancer Evolution Constrained by the Immune MicroenvironmentCell, 2017
- Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancerAnnals Of Oncology, 2016
- Metastatic sites and survival in lung cancerLung Cancer, 2014
- Survival of Patients with Non-Small-Cell Lung Cancer after a Diagnosis of Brain MetastasesCurrent Oncology, 2013