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Brief Report|Articles in Press, 100498

High levels of CD47 expression in thymic epithelial tumors

Open AccessPublished:March 10, 2023DOI:https://doi.org/10.1016/j.jtocrr.2023.100498
High levels of CD47 expression in thymic epithelial tumors
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      ABSTRACT

      Background

      CD47 is a tumor antigen that inhibits phagocytosis leading to immune evasion. Anti-CD47 therapy is a promising new immunotherapy across numerous tumor types but have not been tested in thymic epithelial tumors (TETs)—thymoma and thymic carcinoma. TETs are rare tumors which are difficult to treat, especially with PD-1/PD-L1 checkpoint inhibitors, due to the excessive rates of immune-related adverse events. This study investigated the levels of CD47 expression in TETs to explore the possibility of anti-CD47 therapy.

      Methods

      A total of 67 thymic tumors (63 thymomas and 4 thymic carcinomas) and 14 benign thymus controls, and their clinical data were included. Samples were stained for CD47 expression (rabbit monoclonal antibody SP279, Abcam, USA) and scored for both intensity and H-score (intensity multiplied by the percentage of tumor involved). Intensity was defined as: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. H-scores ranged from 0 to 300. Samples with an intensity score below 2 or an H-score below 150 were considered CD47low, while the rest were CD47high.

      Results

      Compared to normal thymic tissue, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was positive in 79.1% of TETs compared to 57.1% of normal thymus. The level of CD47 expression was 16-fold higher in TETs (mean H-score 75.0 vs 4.6, p = 0.003). Multivariate analysis adjusted for age, sex, stage, resection status, and performance status showed that CD47-high tumors were highly correlated with WHO histology (p = 0.028). The most frequent CD47high tumors, in contrast to CD47low tumors, were types A (28.6% vs 7.5%) and AB (57.1% vs 13.2%), and the least frequent were B1 (7.1% vs 24.5%), B2 (0% vs 35.8%), B3 (7.1% vs 11.3%) and C (0% vs 7.5%).

      Conclusions

      In contrast to normal thymus, TETs had significantly higher levels of CD47 expression. Tumor samples with high CD47 expression were mostly WHO types A and AB. This is the first study to explore CD47 expression in thymic cancers, and lends support for ongoing investigation of anti-CD47 macrophage checkpoint inhibitor therapy in these tumors.

      Keywords

      Article info

      Publication history

      Accepted: March 3, 2023
      Received in revised form: February 27, 2023
      Received: November 21, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Disclosures: Dr. Sun reports personal fees from Frazier Life Sciences Management. Dr. Padda reports personal fees from Mirati, Nanobiotix, Sanofi Genzyme, Rayze Biotech, Genetech, Astrazeneca, Janssen Pharma, Blueprint, G1 Therapeutic, Pfizer. She also participates on an advisory board for the International Association of Lung Cancer. Dr. Natkuman reports personal fees from Leica Biosciences and Roche. Dr. Neal reports grants and personal fees from Takeda; personal fees from AstraZeneca, grants, personal fees, and non-financial support from Genentech/Roche, grants, personal fees, and non-financial support from Exelixis, personal fees from Jounce Therapeutics, personal fees from Eli Lilly and Company, personal fees from Calithera Biosciences, personal fees from Amgen, personal fees from Iovance Biotherapeutics, personal fees from Blueprint Pharmaceuticals, personal fees from Regeneron Pharmaceuticals, personal fees from Natera, personal fees from Surface Oncology, personal fees from D2G Oncology, personal fees from Sanofi Genzyme, personal fees from Turning Point Therapeutics, personal fees from Mirati Therapeutics, personal fees from Gilead, grants and non-financial support from Merck, grants and non-financial support from Novartis, grants and non-financial support from Boehringer Ingelheim, grants and non-financial support from Nektar Therapeutics, grants and non-financial support from Adaptimmune, grants and non-financial support from GSK, grants and non-financial support from Janssen, and grants and non-financial support from AbbVie outside the submitted work. Dr. Wakelee reports research funding from ACEA Biosciences, Arrvs Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, and Helsinn. She also participates on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Merck, Genentch/Roche, International Association for the Study of Lung Cancer, and ECOG-ACRIN. Dr. Riess reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Revolution Medicines, Arrivent and Spectrum; consulting fees from Blueprint, Boehringer Ingelheim, EMD Serono, and Novartis; participation on an Advisory Board for Bayer, Beigene, Biodesix, Regeneron, Turning Point, Bristol Myers Squibb, Daiichi Sankyo, Roche/Genentech, Janssen, Jazz Pharmaceuticals, Mervus and Sanofi. The remaining authors declare no conflict of interest.

      Credit Statement

      Thomas Yang Sun: writing-original draft preparation and subsequent revisions, data gathering, data analysis, investigation

      Brandon Nguyen: data analysis, data gathering

      Simon B. Chen: pathology review, manuscript review

      Yasodha Natkunam: pathology review, tissue microarray creation, manuscript review

      Sukhmani Padda: database curation, manuscript review

      Matt van de Rijn: tissue microarray creation

      Robert West: tissue microarray creation

      Joel W. Neal: data gathering, manuscript review

      Heather Wakelee: manuscript review, supervision

      Jonathan W. Riess: conception, supervision, manuscript review, data analysis

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2023.100498

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      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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