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.
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Data availability
The datasets used during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ICI:
-
Immune checkpoint inhibitor
- TIL:
-
Tumor-infiltrating lymphocyte
- TME:
-
Tumor microenvironment
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Dr. Mansfield was supported by National Institutes of Health Grant P30CA015083.
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All authors contributed to the study conception and design. Material preparation and data collection were performed by Marie Christine Aubry. Data analysis were performed Jarrett Failing and Aaron Mansfield. The first draft of the manuscript was written by Jarrett Failing and all authors revised the manuscript. All authors read and approved the final manuscript.
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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.
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The study was approved by the Mayo Clinic’s Institutional Review Board (IRB #13-007990).
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Failing, J.J., Aubry, M.C. & Mansfield, A.S. Human leukocyte antigen expression in paired primary lung tumors and brain metastases in non-small cell lung cancer. Cancer Immunol Immunother 70, 215–219 (2021). https://doi.org/10.1007/s00262-020-02677-7
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DOI: https://doi.org/10.1007/s00262-020-02677-7