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Heterogeneity of PD-L1 expression between invasive and lepidic components of lung adenocarcinomas

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Abstract

The dynamics of PD-L1 expression are poorly understood over the development of lung adenocarcinomas from pre-invasive lesions to fully invasive carcinomas. Given the importance of PD-L1 expression for the selection of patients to receive immunotherapy in the metastatic setting and possibly in the neoadjuvant setting, we sought to evaluate the agreement of PD-L1 expression in invasive and lepidic components of resected tumor specimens. We stained 86 adenocarcinomas for PD-L1 using the SP263 clone. We assessed the agreement of PD-L1 expression by tumor cells and immune cells between lepidic and invasive components. When both lepidic and invasive components were considered, PD-L1 positive immune cells and tumor cells were observed in 50 (58.1%) and 18 (20.9%) samples, respectively, using a ≥ 1% PD-L1 expression cutoff. Using a ≥ 1% cutoff for PD-L1 expression, positively stained tumor cells were observed in 11 (13%) lepidic and 15 (17%) invasive patterns, with agreement in 76 (88%) specimens and disagreement in 10 (12%) specimens (ĸ = 0.549). At ≥ 1% PD-L1 expression cutoff, PD-L1 positive immune cells were observed in 31 (35%) lepidic and 32 (37%) invasive patterns with an agreement of PD-L1 expression in 49 (57%) specimens and disagreement in 37 (43%) specimens (ĸ = 0.073). In our study of early stage adenocarcinomas of the lung, there was poor agreement in PD-L1 expression between paired invasive and lepidic components of tumors. Our data suggest that the non-invasive tumor components may not be as immunostimulatory as the invasive components, resulting in less adaptive expression of PD-L1.

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Authors and Affiliations

  1. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Antonious Hazim

  2. Division of Oncology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA

    Neil Majithia & Aaron S. Mansfield

  3. Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA

    Stephen J. Murphy

  4. Division of General Thoracic Surgery, Department of Surgery, Rochester, MN, USA

    Dennis Wigle

  5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Marie-Christine Aubry

Authors
  1. Antonious Hazim
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  2. Neil Majithia
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  3. Stephen J. Murphy
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  4. Dennis Wigle
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  5. Marie-Christine Aubry
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  6. Aaron S. Mansfield
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Correspondence to Aaron S. Mansfield.

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Hazim, A., Majithia, N., Murphy, S.J. et al. Heterogeneity of PD-L1 expression between invasive and lepidic components of lung adenocarcinomas. Cancer Immunol Immunother 70, 2651–2656 (2021). https://doi.org/10.1007/s00262-021-02883-x

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  • DOI: https://doi.org/10.1007/s00262-021-02883-x

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